Xinghong Jiang

Nantong University, Tungchow, Jiangsu Sheng, China

Are you Xinghong Jiang?

Claim your profile

Publications (19)77.85 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Ca(2+) plays a key role in intracellular signaling and controls various cellular processes such as proliferation, differentiation, cell growth, death, and apoptosis. Aberrant changes in intracellular Ca(2+) levels can promote undesired cell proliferation and migration and are therefore associated with certain tumor types. Many research groups have suggested a potential role for voltage-gated Ca(2+) channels in the regulation of tumor growth and progression, particularly T-type channels due to their unique biophysical properties. T-type channels are expressed in normal tissues throughout the body and in different types of tumors such as breast carcinoma, retinoblastoma, neuroblastoma, and glioma. It has been demonstrated that increased functional expression of the α1 subunit of T-type channels plays a role in the abnormal proliferation of glioblastoma cells. As such, siRNA-mediated knockdown of the expression of the α1 subunit of T-type channels decreases the proliferation of these cells. Moreover, pharmacological blockade of T-type channels significantly decreases tumor growth. In this review, we focus on the use of T-type channel blockers for the potential treatment of cancers, particularly highly proliferative tumors such as glioblastoma. We conclude that T-type channel blockers such as endostatin can serve as a potential therapeutic tool for tumors whose proliferation depends on increased T-type channel expression.
    Pflügers Archiv - European Journal of Physiology 01/2014; · 4.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Patients with long-standing diabetes frequently demonstrate gastric hypersensitivity with an unknown mechanism. The present study was designed to investigate roles for nuclear factor-κB (NF-κB) and the endogenous H2S-producing enzyme cystathionine-β-synthetase (CBS) signaling pathways by examining cbs gene methylation status in adult rats with diabetes. Intraperitoneal injection of streptozotocin (STZ) produced gastric hypersensitivity in female rats in response to gastric balloon distention. Treatment with the CBS inhibitor aminooxyacetic acid significantly attenuated STZ-induced gastric hypersensitivity in a dose-dependent fashion. Aminooxyacetic acid treatment also reversed hyperexcitability of gastric-specific dorsal root ganglion (DRG) neurons labeled by the dye DiI in diabetic rats. Conversely, the H2S donor NaHS enhanced neuronal excitability of gastric DRG neurons. Expression of CBS and p65 were markedly enhanced in gastric DRGs in diabetic rats. Blockade of NF-κB signaling using pyrrolidine dithiocarbamate reversed the upregulation of CBS expression. Interestingly, STZ treatment led to a significant demethylation of CpG islands in the cbs gene promoter region, as determined by methylation-specific PCR and bisulfite sequencing. STZ treatment also remarkably downregulated the expression of DNA methyltransferase 3a and 3b. More importantly, STZ treatment significantly enhanced the ability of cbs to bind DNA at the p65 consensus site, as shown by chromatin immunoprecipitation assays. Our findings suggest that upregulation of cbs expression is attributed to cbs promoter DNA demethylation and p65 activation and that the enhanced interaction of the cbs gene and p65 contributes to gastric hypersensitivity in diabetes. This finding may guide the development and evaluation of new treatment modalities for patients with diabetic gastric hypersensitivity.
    Journal of Neuroscience 05/2013; 33(21):9028-9038. · 6.91 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The pathogenesis of pain in irritable bowel syndrome (IBS) is poorly understood and treatment remains difficult. We have previously reported that colon-specific dorsal root ganglion (DRG) neurons were hyperactive in a rat model of IBS induced by neonatal colonic inflammation (NCI). This study was designed to examine plasticity of voltage-gated sodium channel activities and roles for endogenous hydrogen sulfide producing enzyme cystathionine β-synthetase (CBS) in chronic visceral hyperalgesia. Abdominal withdrawal reflex (AWR) scores were recorded in response to graded CRD in adult male rats as a measure of visceral hypersensitivity. Colon-specific DRG neurons were labeled with DiI and acutely dissociated for measuring sodium channel currents. Western blot analysis was employed to detect changes in expressions of Nav1.7, Nav1.8 and CBS. NCI significantly increased AWR scores when compared with age-matched controls. NCI also led to a ~2.5 fold increase in sodium current density in colon-specific DRG neurons. Furthermore, NCI dramatically enhanced expression of Nav1.7, NaV1.8 and CBS in colon related DRGs. CBS was colocalized with NaV1.7 or 1.8 in colon-specific DRG neurons. Administration of O-(Carboxymethyl) hydroxylamine hemihydrochloride (AOAA), an inhibitor for CBS, remarkably suppressed sodium current density and reduced expression of Nav1.7 and NaV1.8. More importantly, intraperitoneal or intrathecal application of AOAA attenuated AWR scores in NCI rats, in a dose-dependent manner. These data suggest that NCI enhances sodium channel activity of colon DRG neurons, which is most likely mediated by upregulation of CBS expression, thus identifying a potential target for treatment for chronic visceral pain in patients with IBS.
    AJP Gastrointestinal and Liver Physiology 02/2013; · 3.65 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Hydrogen sulfide (H2S), an endogenous gaseotransmitter/modulator, is becoming appreciated that it may be involved in a wide variety of processes including inflammation and nociception. However, the role and mechanism for H2S in nociceptive processing in trigeminal ganglion (TG) neuron remains unknown. The aim of this study is to investigate distribution of endogenous H2S synthesizing enzyme cystathionine-beta-synthetase (CBS) expression and role of H2S on excitability and voltage-gated potassium channels of TG neurons. METHODS: Immunofluorescence studies were carried out to determine whether CBS was co-expressed in Kv1.1 or Kv1.4-positive TG neurons. Whole cell patch clamp recordings were employed on acutely isolated TG neurons from adult male Sprague Dawley rats (6--8 week old). von Frey filaments were used to examine the pain behavioral responses in rats following injection of sodium hydrosulfide. RESULTS: In rat TG, 77.0+/-6.6% neurons were immunoreactive for CBS, 85.1+/-3.8% for Kv1.1 and 97.8+/-1.1% for Kv1.4. Double staining showed that all CBS labeled cells were Kv1.1 and Kv1.4 positive, but only 92.2+/-6.1% of Kv1.1 and 78.2+/-9.9% of Kv1.4 positive cells contained CBS. Application of H2S donor NaHS (250 muM) led to a significant depolarization of resting membrane potential recorded from TG neurons. NaHS application also resulted in a dramatic reduction in rheobase, hyperpolarization of action potential threshold, and a significant increase in the number of action potentials evoked at 2X and 3X rheobase stimulation. Under voltage-clamp conditions, TG neurons exhibited transient A-type (IA) and sustained outward rectifier K+ currents (IK). Application of NaHS did suppress IK density while did not change IA density of TG neurons (n=6). Furthermore, NaHS, a donor of hydrogen sulfide, produced a significant reduction in escape threshold in a dose dependent manner. CONCLUSION: These data suggest that endogenous H2S generating enzyme CBS was co-localized well with Kv1.1 and Kv1.4 in TG neurons and that H2S produces the mechanic pain and increases neuronal excitability, which might be largely mediated by suppressing IK density, thus identifying for the first time a specific molecular mechanism underlying pain and sensitization in TG.
    Molecular Pain 02/2013; 9(1):4. · 3.77 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hydrogen sulfide (H(2)S), an endogenous gas molecule synthesized by cystathionine-β-synthetase (CBS), is involved in inflammation and nociceptive signaling. However, the molecular and epigenetic mechanisms of CBS-H(2)S signaling in peripheral nociceptive processing remain unknown. We demonstrated that peripheral inflammation induced by intraplantar injection of complete Freund adjuvant significantly up-regulated expression of CBS at both protein and mRNA levels in rat dorsal root ganglia (DRG). The CBS inhibitors hydroxylamine and aminooxyacetic acid attenuated mechanical hyperalgesia in a dose-dependent manner and reversed hyperexcitability of DRG neurons in inflamed rats. Intraplantar administration of NaHS (its addition mimics CBS production of H(2)S) or l-cysteine in healthy rats elicited mechanical hyperalgesia. Application of NaHS in vitro enhanced excitability and tetrodotoxin (TTX)-resistant sodium current of DRG neurons from healthy rats, which was attenuated by pretreatment of protein kinase A inhibitor H89. Methylation-specific PCR and bisulfite sequencing demonstrated that promoter region of cbs gene was less methylated in DRG samples from inflamed rats than that from controls. Peripheral inflammation did not alter expression of DNA methyltransferase 3a and 3b, the 2 major enzymes for DNA methylation, but led to a significant up-regulation of methyl-binding domain protein 4 and growth arrest and DNA damage inducible protein 45α, the enzymes involved in active DNA demethylation. Our findings suggest that epigenetic regulation of CBS expression may contribute to inflammatory hyperalgesia. H(2)S seems to increase TTX-resistant sodium channel current, which may be mediated by protein kinase A pathway, thus identifying a potential therapeutic target for the treatment of chronic pain.
    Pain 01/2013; 154(1):34-45. · 5.64 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Irritable bowel syndrome (IBS) is characterized by chronic visceral hyperalgesia (CVH) that manifested with persistent or recurrent abdominal pain and altered bowel movement. However, the pathogenesis of the CVH remains unknown. The aim of this study was to investigate roles of endogenous hydrogen sulfide (H2S) producing enzyme cystathionine beta-synthetase (CBS) and p65 nuclear factor-kappa B subunits in CVH. RESULTS: CVH was induced by neonatal maternal deprivation (NMD) in male rats on postnatal days 2--15 and behavioral experiments were conducted at the age of 7--15 weeks. NMD significantly increased expression of CBS in colon-innervating DRGs from the 7th to 12th week. This change in CBS express is well correlated with the time course of enhanced visceromoter responses to colorectal distention (CRD), an indicator of visceral pain. Administration of AOAA, an inhibitor of CBS, produced a dose-dependent antinociceptive effect on NMD rats while it had no effect on age-matched healthy control rats. AOAA also reversed the enhanced neuronal excitability seen in colon-innervating DRGs. Application of NaHS, a donor of H2S, increased excitability of colon-innervating DRG neurons acutely dissociated from healthy control rats. Intrathecal injection of NaHS produced an acute visceral hyperalgesia. In addition, the content of p65 in nucleus was remarkably higher in NMD rats than that in age-matched controls. Intrathecal administration of PDTC, an inhibitor of p65, markedly reduced expression of CBS and attenuated nociceptive responses to CRD. CONCLUSION: The present results suggested that upregulation of CBS expression, which is mediated by activation of p65, contributes to NMD-induced CVH. This pathway might be a potential target for relieving CVH in patients with IBS.
    Molecular Pain 12/2012; 8(1):89. · 3.77 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by abdominal pain in association with altered bowel movements. The underlying mechanisms of visceral hypersensitivity remain elusive. This study was designed to examine the role for sodium channels in a rat model of chronic visceral hyperalgesia induced by neonatal maternal deprivation (NMD). Abdominal withdrawal reflex (AWR) scores were performed on adult male rats. Colon-specific dorsal root ganglion (DRG) neurons were labeled with DiI and acutely dissociated for measuring excitability and sodium channel current under whole-cell patch clamp configurations. The expression of NaV1.8 was analyzed by western blot and quantative real time-PCR. NMD significantly increased AWR scores, which lasted for ~6 weeks in an association with hyperexcitability of colon DRG neurons. TTX-resistant but not TTX-sensitive sodium current density was greatly enhanced in colon DRG neurons in NMD rats. Compared with controls, activation curve showed a leftward shift in NMD rats while inactivation curves did not differ significantly. NMD markedly accelerated the activation time of peak current amplitude without any changes in inactivation time. Furthermore, NMD remarkably enhanced expression of NaV1.8 at protein levels but not at mRNA levels in colon related DRGs. The expression of NaV1.9 was not altered after NMD. These data suggest that NMD enhances TTX-resistant sodium activity of colon DRG neurons, which is most likely mediated by a leftward shift of activation curve and by enhanced expression of NaV1.8 at protein levels, thus identifying a specific molecular mechanism underlying chronic visceral pain and sensitization in patients with IBS.
    AJP Gastrointestinal and Liver Physiology 11/2012; · 3.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The tyrosine kinases of Src family play an important role in the central sensitization following peripheral inflammation. However, whether Src family in the arcuate nucleus (ARC) of mediobasal hypothalamus is involved in central sensitization remains unknown. The aim of this study was to investigate the role and mechanisms of tyrosine kinases of Src family in NMDA receptor activity in the ARC following peripheral inflammation. Peripheral inflammation was induced by unilateral injection of complete Freund's adjuvant (CFA) into rat hind paw. The neuronal activities of ARC were recorded using electrophysiological field recording from the in vitro mediobasal hypothalamic slices from control and CFA rats. Expression of total and phosphorylated Src and NR2B subunit protein was analyzed by western blot and immuoprecipitation. Our results showed that CFA injection resulted in an increase in mechanical and thermal sensitivity, which was partially blocked by neonatal monosodium glutamate treatment. CFA injection also enhanced spontaneous firings of ARC neurons, which were reversed by an NMDA receptor NR2B subunit specific antagonist Ro25-6981 and by PP2, an Src family tyrosine kinase inhibitor. In addition, peripheral inflammation enhanced Src phosphorylation and NMDA receptor NR2B subunit phosphorylation without alteration of total NR2B subunit expression in ARC. Peripheral inflammation also increased the association of NR2B protein with p-Src protein in ARC. Administration of PP2 blocked the upregulation of NR2B phosphorylation induced by CFA injection. Taken together, our present results suggest that the arcuate Src activation-induced tyrosine phosphorylation of NR2B NMDA subunit may contribute to inflammatory pain.
    Journal of Neurophysiology 09/2012; · 3.30 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Low-voltage-activated T-type Ca(2+) channels contribute to a wide variety of physiological functions, most predominantly in the nervous, cardiovascular and endocrine systems. Studies have documented the roles of T-type channels in sleep, neuropathic pain, absence epilepsy, cell proliferation and cardiovascular function. Importantly, novel aspects of the modulation of T-type channels have been identified over the last few years, providing new insights into their physiological and pathophysiological roles. Although there is substantial literature regarding modulation of native T-type channels, the underlying molecular mechanisms have only recently begun to be addressed. This review focuses on recent evidence that the Cav3 subunits of T-type channels, Cav3.1, Cav3.2 and Cav3.3, are differentially modulated by a multitude of endogenous ligands including anandamide, monocyte chemoattractant protein-1, endostatin, and redox and oxidizing agents. The review also provides an overview of recent knowledge gained concerning downstream pathways involving G-protein-coupled receptors. This article is part of a Special Issue entitled: Calcium channels.
    Biochimica et Biophysica Acta 09/2012; · 4.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although neuromedin U (NMU) has been implicated in analgesia, the detailed mechanisms still remain unclear. In this study, we identify a novel functional role of NMU type 1 receptor (NMUR1) in regulating the transient outward K(+) currents (I(A)) in small dorsal root ganglion (DRG) neurons. We found that NMU reversibly increased I(A) in a dose-dependent manner, instead the sustained delayed rectifier K(+) current (I(DR)) was not affected. This NMU-induced I(A) increase was pertussis toxin-sensitive and was totally reversed by NMUR1 knockdown. Intracellular application of GDPβS (guanosine 5'-O-(2-thiodiphosphate)), QEHA peptide, or a selective antibody raised against the Gα(o) or Gβ blocked the stimulatory effects of NMU. Pretreatment of the cells with the protein kinase A (PKA) inhibitor or ERK inhibitor abolished the NMU-induced I(A) response, whereas inhibition of phosphatidylinositol 3-kinase or PKC had no such effects. Exposure of DRG neurons to NMU markedly induced the phosphorylation of ERK (p-ERK), whereas p-JNK or p-p38 was not affected. Moreover, the NMU-induced p-ERK increase was attenuated by PKA inhibition and activation of PKA by foskolin would mimic the NMU-induced I(A) increase. Functionally, we observed a significant decrease of the firing rate of neuronal action potential induced by NMU and pretreatment of DRG neurons with 4-AP could abolish this effect. In summary, these results suggested that NMU increases I(A) via activation of NMUR1 that couples sequentially to the downstream activities of Gβγ of the G(o) protein, PKA, and ERK, which could contribute to its physiological functions including neuronal hypoexcitability in DRG neurons.
    Journal of Biological Chemistry 04/2012; 287(22):18562-72. · 4.65 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hydrogen sulfide (H(2)S) functions as a neuromodulator, but whether it modulates visceral pain is not well known. This study was designed to determine the role for the endogenous H(2)S producing enzyme cystathionine β-synthetase (CBS) and cystathionine γ-lyase (CSE) in a validated rat model of visceral hyperalgesia (VH). VH was induced by nine-day heterotypic intermittent stress (HIS). Abdominal withdrawal reflex (AWR) scores were determined by measuring the visceromoter responses to colorectal distension (CRD). Dorsal root ganglia (DRG) neurons innervating the colon were labeled by injection of DiI (1,1'-dioleyl-3,3,3',3-tetramethylindocarbocyanine methanesulfonate) into the colon wall. Patch clamp recording techniques were employed to examine excitability and sodium channel currents of colon specific DRG neurons. Tissues from colon related thoracolumbar DRGs were analyzed for CBS, CSE and sodium channel expression. HIS significantly increased the visceromotor responses to CRD in association with an upregulated expression of CBS not CSE proteins in colon related DRGs. Administration of O-(Carboxymethyl)hydroxylamine hemihydrochloride (AOAA), an inhibitor of CBS, attenuated the AWR scores in HIS-treated rats, in a dose dependent fashion. In contrast, AOAA did not produce any effect on AWR scores in healthy control rats. AOAA reversed the potentiation of sodium channel current densities of colon specific DRG neurons of HIS rats. To further confirm the role for CBS-H(2)S signaling, NaHS was used to mimic the production of H(2)S by CBS. Application of NaHS significantly enhanced neuronal excitability and potentiated sodium channel current densities of colon DRG neurons from healthy control rats. Furthermore, AOAA reversed the upregulation of Na(V)1.7 and Na(V)1.8 in colon related DRGs of HIS rats. Our results suggest that upregulation of CBS expression might play an important role in developing VH via sensitization of sodium channels in peripheral nociceptors, thus identifying a specific neurobiological target for the treatment of VH in functional bowel syndromes.
    PLoS ONE 01/2012; 7(12):e53165. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The long-chain neurotoxic protein, alpha-cobratoxin (α-CTx), has been shown to have analgesic effects. However, the underlying mechanisms still remain unclear. In this study, we examined the effects of α-CTx on T-type calcium channel currents (T-currents) and elucidated the relevant mechanisms in mouse dorsal root ganglion (DRG) neurons. Our results showed that α-CTx reversibly inhibited T-currents in a dose-dependent manner. This inhibitory effect was blocked by the selective muscarinic M4 receptor antagonist tropicamide, while methyllycaconitine, a specific antagonist for the α7 subtype of nicotinic receptor had no effect. siRNA targeting the M4 receptor in small DRG neurons abolished α-CTx-induced T-current inhibition. Intracellular application of GDP-β-S or a selective antibody against the G(o)α-protein, as well as pretreatment of the cells with pertussis toxin, abolished the inhibitory effects of α-CTx. The M4 receptor-mediated response was blocked by dialyzing cells with QEHA peptide or anti-G(β) antibody. Pretreatment of the cells with protein kinase A (PKA) inhibitor H89 or intracellular application of PKI 6-22 abolished α-CTx-induced T-current inhibition in small DRG neurons, whereas inhibition of phosphatidylinositol 3-kinase or PKC elicited no such effects. In addition, α-CTx significantly increased PKA activity in DRG neurons, whereas pretreatment of the cells with tropicamide abolished this effect. In summary, our results suggest that activation of muscarinic M4 receptor by α-CTx inhibits T-currents via the G(βγ) of G(o)-protein and PKA-dependent pathway. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.
    Neuropharmacology 11/2011; 62(2):1062-72. · 4.11 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cobrotoxin (CbT), a short-chain postsynaptic α-neurotoxin, has been reported to play a role in analgesia. However, to date, the detailed mechanisms still remain unknown. In the present study, we identify a novel functional role of CbT in modulating T-type Ca(2+) channel currents (T-currents) in small dorsal root ganglia (DRG) neurons as well as pain behaviors in mice. We found that CbT inhibited T-currents in a dose-dependent manner. CbT at 1μM reversibly inhibited T-currents by ~26.3%. This inhibitory effect was abolished by the non-selective muscarinic acetylcholine receptor (mAChR) antagonist atropine, or the selective M3 mAChR antagonist 4-DAMP, while naloxone, an opioid receptor antagonist had no effect. Intracellular infusion of GDP-β-S or pretreatment of the cells with pertussis toxin (PTX) completely blocked the inhibitory effects of CbT. Using depolarizing prepulse, we found the absence of direct binding between G-protein βγ subunits and T-type Ca(2+) channels in CbT-induced T-current inhibition. CbT responses were abolished by the phospholipase C inhibitor U73122 (but not the inactive analog U73343). The classical and novel protein kinase C (nPKC) antagonist chelerythrine chlorid or GF109203X abolished CbT responses, whereas the classical PKC antagonist Ro31-8820 or inhibition of PKA elicited no such effects. Intrathecal administration of CbT (5μg/kg) produced antinociceptive effects in mechanical, thermal, and inflammatory pain models. Moreover, CbT-induced antinociception could be abrogated by 4-DAMP. Taken together, these results suggest that CbT acting through M3 mAChR inhibits T-currents via a PTX-sensitive nPKC pathway in small DRG neurons, which could contribute to its analgesic effects in mice.
    Cellular Signalling 02/2011; 23(6):1057-67. · 4.47 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Neuromedin U (NMU) has recently been reported to play a role in nociception. However, to date, the relevant mechanisms still remain unknown. In the present study, we investigated the expression profile of NMU receptors in mouse dorsal root ganglia (DRG) and identified a novel functional role of NMU in modulating T-type Ca(2+) channel currents (T-currents) as well as membrane excitability in small DRG neurons. We found that NMU inhibited T-currents in a dose-dependent manner in mouse small DRG neurons that endogenously expressed NMU type 1 (NMUR1), but not NMUR2 receptors. NMU (1μM) reversibly inhibited T-currents by ∼27.4%. This inhibitory effect was blocked by GDP-β-S or pertussis toxin (PTX), indicating the involvement of a G(i/o)α-protein. Using depolarizing prepulse or intracellular application of QEHA, a synthetic peptide which competitively blocks G-protein βγ subunit (G(βγ)) mediated signaling, we found the absence of functional coupling between G(βγ) and T-type Ca(2+) channels. Pretreatment of the cells with H89, a protein kinase A (PKA) inhibitor, or intracellular application of PKI 5-24, blocked NMU-induced T-current inhibition, whereas inhibition of phospholipase C or protein kinase C elicited no such effects. In addition, we observed a significant decreased firing frequency of action potentials of small DRG neurons induced by NMU, which could be abrogated by pretreatment of the cells with NiCl(2) (100 μM). Taken together, these results suggested that NMU inhibits T-currents via PTX-sensitive PKA pathway, which might contribute to its physiological functions including neuronal hypoexcitability in small DRG neurons in mice.
    Cell calcium 01/2011; 49(1):12-22. · 4.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Neuromedin U (NMU) plays very important roles in the central nervous system. However, to date, any role of NMU in hippocampal neurons and the relevant mechanisms still remain unknown. In the present study, we report that NMU selectively inhibits L-type high-voltage-gated Ca(2+) channels (HVGCC) in mouse hippocampal neurons, in which NMU type 1 receptor (NMUR1), but not NMUR2, is endogenously expressed. In wild type mice, NMU (0.1 microM) reversibly inhibited HVGCC barium currents (I(Ba)) by approximately 28%, while in NMUR1(-/-) mice NMU had no significant effects. Intracellular infusion of GDP-beta-S or a selective antibody raised against the G(o)alpha, as well as pretreatment of the neurons with pertussis toxin, blocked the inhibitory effects of NMU, indicating the involvement of G(o)-protein. This NMUR1-mediated effect did not display the characteristics of a direct interaction between G-protein betagamma subunit (G(betagamma)) and L-type HVGCC, but was abolished by dialyzing cells with QEHA peptide or an antibody to the G(beta). The classical and novel protein kinase C (PKC) antagonist calphostin C, as well as phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, abolished NMU responses, whereas the classical PKC antagonist Gö6976 had no such effects. Cells dialyzed with a PKC epsilon isoform (PKCepsilon) specific inhibitor peptide, GAVSLLPT, abolished NMU responses. In contrast, in cells dialyzed with an inactive PKCepsilon control scramble peptide, LSGTLPAV, no significant effects were observed. In summary, these results suggest that NMU inhibits L-type HVGCC via activation of NMUR1 and downstream G(betagamma), PI3K, and a novel PKCepsilon signaling pathway.
    Cellular Signalling 11/2010; 22(11):1660-8. · 4.47 Impact Factor
  • Source
    Guang-Yin Xu, Fen Wang, Xinghong Jiang, Jin Tao
    [Show abstract] [Hide abstract]
    ABSTRACT: The pathophysiology of migraine remains largely unknown. However, evidence regarding the molecules participating in the pathophysiology of migraine has been accumulating. Water channel proteins, known as aquaporins (AQPs), notably AQP-1 and AQP-4, appears to be involved in the pathophysiology of several neurological diseases. This review outlines newly emerging evidence indicating that AQP-1 plays an important role in pain signal transduction and migraine and could therefore serve as a potential therapeutic target for these diseases.
    Molecular Pain 10/2010; 6:68. · 3.77 Impact Factor
  • Yi Che, Rui Xing, Yufang Zhu, Yonghua Cui, Xinghong Jiang
    [Show abstract] [Hide abstract]
    ABSTRACT: Lanthanum cations are well known for their inhibitory actions on calcium channels, and calcium cations are indispensable for the development of brain. Lanthanum may interfere with the developing central nervous system. Detour learning task in chicks is an excellent model to study the development of central nervous system. In the present study, we examined the effects of lanthanum chloride exposure on the development of spatial cognition using the detour learning task. The data suggest that the chicks injected with lanthanum chloride (10 or 5 mM) had significantly delayed the response latency of detour learning but not the chicks injected with lanthanum chloride (1 mM). The effect of lanthanum exposure on the development of spatial cognition is dose relative.
    Biological trace element research 09/2010; 143(1):274-80. · 1.92 Impact Factor
  • Jin Tao, Yuan Zhang, Hua Huang, Xinghong Jiang
    [Show abstract] [Hide abstract]
    ABSTRACT: Corticotropin-releasing factor (CRF) receptors have been demonstrated to be widely expressed in the central nervous system and in many peripheral tissues of mammalians. However, it is still unknown whether CRF receptors will function in cerebellar Purkinje neurons. In the present study, we investigated the expression profile of CRF receptors in rat cerebellum and identified a novel functional role of CRFR2 in modulating Purkinje neuron P-type Ca(2+) currents (P-currents). We found that CRFR2alpha mRNA, but not CRFR1 and CRFR2beta, was endogenously expressed in rat cerebellum. Activation of CRFR2 by UCN2 inhibited P-currents in a concentration-dependent manner (IC(50) approximately 0.07 microM). This inhibitory effect was abolished by astressin2B, a CRFR2 antagonist, and was blocked by GDP-beta-S, pertussis toxin, or a selective antibody raised against the G(o)alpha. Inhibition of phospholipase C (PLC) blocked the inhibitory action of UCN2. The application of diacylglycerol (DAG) antagonist, 1-hexadecyl-2-acetyl-sn-glycerol, as well as inhibition of either protein kinase C or its epsilon isoform (PKCepsilon) abolished the UCN2 effect while 1-oleoyl-2-acetyl-sn-glycerol (EI-150), a membrane-permeable DAG analogue, occluded UCN2-mediated inhibition. In addition, UCN2 significantly increases spontaneous firing frequency of Purkinje neurons in cerebellar slices. In summary, activation of CRFR2 inhibits P-currents in Purkinje neurons via G(o)alpha-dependent PLC/PKCepsilon pathway, which might contribute to its physiological functions in the cerebellum.
    Cellular Signalling 06/2009; 21(9):1436-43. · 4.47 Impact Factor
  • Yi Che, Yonghua Cui, Xinghong Jiang
    [Show abstract] [Hide abstract]
    ABSTRACT: Lanthanum cations (La 3+) are well known for their inhibitory actions on calcium channels. Prenatal lanthanum exposure may affect the development of embryo and alter the capacity for learning and memory in adults, and the one-trial passive avoidance learning paradigm with day-old chicks is an excellent model to study several mechanisms of memory formation. In the present study, we examined the effects of prenatal lanthanum chloride exposure on memory consolidation using one-trial passive avoidance learning task in day-old chicks. The data suggest that chicks injected with lanthanum chloride (2 mg/kg) daily from E9 to E16 had significantly impaired long-term memory at 120 min after training (p < 0.05) but not the chicks injected with lanthanum chloride (0.1 mg/kg) daily from E9 to E16.
    Biological trace element research 10/2008; 127(1):37-44. · 1.92 Impact Factor