
Ashok Srivastava- National Council of Educational Research and Training
Ashok Srivastava
- National Council of Educational Research and Training
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Publications (102)
Nitric oxide (NO) is a diffusible free radical and universal messenger that is produced from L-arginine by three different isoforms of nitric oxide synthases (NOS), neuronal (nNOS), inducible (iNOS) and endothelial NOS (eNOS). NO plays an important role in the regulation of variety of physiological functions including myocardial contractility, vasc...
Background:
We recently showed that vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) exhibit overexpression of Sirtuin1 (Sirt1) that contributes to the enhanced expression of Giα proteins implicated in the development of hypertension in SHR.
Method:
The present study investigated if the inhibition of Sirt1 could al...
Background:
We earlier demonstrated that vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) exhibit the overexpression of Giα proteins and hyperproliferation that is attributed to the enhanced levels of endogenous II angiotensin (Ang II). In addition, the implication of Sirtuin1 (Sirt1) a histone deacetylase class III f...
Angiotensin II (Ang II) regulates an array of physiological and pathological responses in vascular smooth muscle cells (VSMCs) by activating ERK1/2 and PI3K/Akt signaling pathways. We have demonstrated that Ang II and insulin-like growth factor-1 (IGF-1) induces the expression of early growth response protein-1 (Egr-1), a zinc finger transcription...
Cyclic AMP response element (CRE) binding protein (CREB) is a nuclear transcription factor that regulates the transcription of several genes containing the CRE sites on their promoters. CREB is activated by phosphorylation on a key serine residue, Ser311, in response to a wide variety of extracellular stimuli including angiotensin II (Ang II). Ang...
Sirtuin‐1 (SIRT1), class III histone deacetylase, has been shown to be overexpressed in hearts from spontaneously hypertensive rats (SHR). We recently showed that vascular smooth muscle cells (VSMC) from SHR exhibit enhanced expression of SIRT1 as compared to age‐matched Wister Kyoto (WKY) rats and contribute to the upregulation of Giα proteins imp...
Angiotensin II (Ang II), a key vasoactive peptide, is known to play an important role in the pathophysiology of vascular diseases. A heightened activation of Ang II‐induced signaling pathways that promote proliferation, hypertrophy and migration of vascular smooth muscle cells (VSMCs) has been suggested to contribute to vascular dysfunctions. We ha...
Increased generation of reactive oxygen species is believed to play a key role in the pathophysiology of cardiovascular diseases. Excessive growth and proliferation of vascular smooth muscle cells (VSMCs) have been suggested to be major contributors to vascular dysfunction. Potential involvement of early growth response protein-1 (Egr-1), a zinc fi...
Augmented levels of angiotensin‐II (Ang‐II) are associated with the development of cardiovascular disorders such as atherosclerosis and hypertension. Exaggerated activation of Ang‐II‐induced signaling events and expression of genes linked to cell proliferation, hypertrophy and migration have been demonstrated to contribute to the development of the...
Insulin‐like growth factor 1 (IGF‐1) mediates the generation of reactive oxygen species (ROS) and the activation of growth promoting signaling pathways. Histone deacetylases (HDACs) regulate gene transcription by deacetylating lysine residues in histone and nonhistone proteins and a heightened HDAC activation, notably of HDAC5, is associated with v...
Increased generation of reactive oxygen species (ROS) is believed to play a key role in the pathophysiology of cardiovascular diseases. Excessive growth and proliferation of vascular smooth muscle cells (VSMC) have been suggested to be major contributors to vascular dysfunction. A potential involvement of early growth response protein‐1 (Egr‐1), a...
Vascular disease represents one of the major complications of diabetes. Chronic or spiking postprandial hyperglycemia- induced increase in protein glycation, oxidative stress, inflammation and alterations in the levels/action of vasoactive peptides and growth factors have been suggested as potential mediators of vascular dysfunction. Phenotypic mod...
cAMP has been shown to inhibit vascular smooth muscle cell proliferation and exerts a vasculoprotective effect. An upregulation of the early growth response protein-1 (Egr-1) expression has been linked with the development of atherosclerosis and intimal hyperplasia. We have recently demonstrated that angiotensin-II (Ang-II) stimulates Egr-1 express...
An upregulation of Egr-1 expression has been reported in models of atherosclerosis and intimal hyperplasia and, various vasoactive peptides and growth promoting stimuli have been shown to induce the expression of Egr-1 in vascular smooth muscle cells (VSMC). Angiotensin-II (Ang-II) is a key vasoactive peptide that has been implicated in the pathoge...
We have previously demonstrated that the non-receptor protein tyrosine kinase (NR-PTK) c-Src is an upstream regulator of endothelin-1 (ET-1) and angiotensin II-induced activation of protein kinase B (PKB) signaling in vascular smooth muscle cells (VSMCs). We have also demonstrated that ET-1 potently induces the expression of the early growth respon...
Insulin‐like growth factor 1 (IGF‐1), a potent mitogenic and vasoactive factor, has been shown to play an important role in the development of cardiovascular diseases. This occurs through the generation of reactive oxygen species (ROS) as well as through the hyperactivation of mitogenic and growth promoting signaling pathways and the subsequent alt...
The early growth response protein 1 (Egr‐1) is a zinc finger transcription factor that has been suggested to regulate the expression of genes linked with inflammation and cell cycle regulation. An up‐regulation of Egr‐1 expression has been reported in models of atherosclerosis and intimal hyperplasia. Various vasoactive peptides and growth promotin...
Early growth response protein-1 (Egr-1) is a transcription factor that plays an important role in the regulation of several genes implicated in the pathogenesis of cardiovascular disease (CVD) such as atherosclerosis. IGF-1, a potent mitogen, is believed to contribute to the development of CVD, such as atherosclerosis, through the hyperactivation o...
Nitric oxide (NO) is a vasoprotective molecule that plays a critical role in modulating endothelial functions. A compromised NO bioavailability due to defective NOgeneration by endothelial nitric oxide synthase (eNOS) has been suggested as one of the mechanisms leading to the pathogenesis ofvascular abnormalities such as atherosclerosis. NO synthes...
Vascular disease as evidenced by aberrant endothelial and vascular smooth muscle cell physiology represents one of the major complications of diabetes. Although the metabolic disturbances such as oxidative stress, inflammation, and hyperlipidemia have been well described as main players in the process of vascular dysfunction, epigenetic modificatio...
Hyperactivation of proliferative and growth promoting pathways underlies the progression of vessel remodeling, leading to vascular dysfunction. An upregulation of early growth response protein 1 (Egr-1), a zinc finger transcription factor has been observed in several models of vascular diseases. In the vasculature, Egr-1 expression can be induced b...
Vasoactive peptides such as angiotensin II and endothelin-1 as well as growth factors regulate vascular homeostasis through signaling pathways that are triggered in both normal and disease states. These vasoactive peptides and growth factors also increase the cellular levels of calcium which, through calcium binding effector systems initiates the d...
Insulin-like growth factor 1 (IGF-1) is a mitogenic factor that stimulates the signaling pathways responsible for inducing hypertrophic and proliferative responses in vascular smooth muscle cells (VSMC). We have previously demonstrated that IGF-1 receptor (IGF-1R) plays a key role in transducing the hypertrophic and proliferative responses of angio...
While it has long been known that zinc (Zn) is crucial for the proper growth and maintenance of normal biological functions, Zn has also been shown to exert insulin-mimetic and anti-diabetic effects. These insulin-like properties have been demonstrated in isolated cells, tissues, and different animal models of type 1 and type 2 diabetes. Zn treatme...
Curcumin is the active component in turmeric--a spice that has been extensively used as a culinary agent and a home remedy to prevent and treat many diseases in India and other countries for hundreds of years. However, systematic studies to understand the molecular basis of disease preventing or therapeutic properties of curcumin began to appear in...
Endothelin-1 (ET-1) is implicated in the pathogenesis of vascular abnormalities through the hyperactivation of growth promoting pathways, including protein kinase B (PKB) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. ET-1 has been shown to elicit its responses through the generation of reactive oxygen species (ROS). Curcumin, th...
ET‐1 is implicated in the pathogenesis of vascular abnormalities, such as hypertension and atherosclerosis, through the hyperactivation of growth promoting signaling pathways such as ERK1/2 and PKB. We have recently shown that CaMKII‐α, a multifunctional protein kinase plays a critical role in mediating ET‐1‐induced ERK1/2 and PKB signaling as well...
Egr‐1 transcription factor plays an important role in vascular biology. Following activation, Egr‐1 is expressed in the nucleus and can regulate transcription of several genes implicated in the development of vascular disease (VD). A potential role of aberrant ET‐1 signaling is thought to contribute to the development of VD, such as atherosclerosis...
Endothelin-1 (ET-1) and angiotensin II (Ang II) play important roles in maintaining blood pressure and vascular homeostasis, and a heightened activity of these vasoactive peptides are thought to contribute to the development of vascular pathologies, such as hypertension, atherosclerosis, hypertrophy, and restenosis. This is caused by an excessive a...
Nitric oxide (NO) is an important vasoprotective molecule that serves not only as a vasodilator but also exerts antihypertrophic and antiproliferative effects in vascular smooth muscle cells (VSMC). The precise mechanism by which the antihypertrophic and antiproliferative responses of NO are mediated remains obscure. However, recent studies have su...
Endothelin-1 (ET-1) is a potent vasoactive peptide that exerts hypertrophic, migratory, and mitogenic effects in vascular smooth muscle cells. ET-1-induced activation of several signaling events has been shown to mediate the cellular effects of ET-1. In the past several years, transactivation of growth factor receptor has gained much recognition in...
Endothelin‐1 (ET‐1) and Angiotensin II (Ang II), two important vasoactive peptides, have been implicated in the pathogenesis of vascular abnormalities such as hypertension and atherosclerosis, through the activation of growth promoting signal transduction pathways, which include mitogen‐activated protein kinases (MAPKs) and phosphatidylinositol 3 k...
Zn2+ exerts insulin-mimetic and antidiabetic effects in rodent models of insulin resistance, and activates extracellular-signal-regulated kinases 1 and 2 (ERK1/2) and protein kinase B (PKB), key components of the insulin signaling pathway. Zn2+-induced signaling has been shown to be associated with an increase in the tyrosine phosphorylation of ins...
Endothelin-1 (ET-1) and angiotensinII (AngII) are vasoactive peptides believed to contribute to the pathogenesis of vascular abnormalities such as hypertension, atherosclerosis, hypertrophy, and restenosis. The concept of transactivation of growth factor receptors, such as epidermal growth factor receptor (EGFR), in triggering vasoactive peptide-in...
Over the last several decades, a large body of evidence has accumulated to suggest that organo-vanadium compounds (OVC) are more potent than inorganic vanadium salts in regulating hyperglycemia and insulin-resistance in rodent models of both type I and type II diabetes. Among these OVC, vanadium (IV) oxo bis(maltolato) (BMOV) was the first to be in...
We have shown earlier a requirement for Ca(2+) and calmodulin (CaM) in the H(2)O(2)-induced activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and protein kinase B (PKB), key mediators of growth-promoting, proliferative, and hypertrophic responses in vascular smooth muscle cells (VSMC). Because the effect of CaM is mediated throu...
Over the past several decades, multiple studies have shown that organo-vanadium compounds (OVC) have more potent anti-diabetic and insulin-mimetic effects than their inorganic vanadium salt counterparts, both in vitro and in vivo. Several of these OVCs, such as Bis(maltolato) Oxo Vanadium (IV) (BMOV) and Bis(alixinato) Oxo Vanadium (IV) (Valx), hav...
Insulin-like growth factor (IGF)-induced signaling networks are vital in modulating multiple fundamental cellular processes, such as cell growth, survival, proliferation, and differentiation. Aberrations in the generation or action of IGF have been suggested to play an important role in several pathological conditions, including metabolic disorders...
Levels of insulin‐signalling molecules are altered in streptozotocin (STZ)‐induced diabetes, a model of Type 1 diabetes. However, the tissue‐specific regulation of these changes and the effect of insulin supplementation on signalling molecule protein levels have not been well characterized.
In the present study, we evaluated the level of proximal i...
Vanadium is a trace element of ubiquitous occurrence. Vanadium compounds have been shown to exert a variety of insulin-like effects both in vitro and in vivo. These effects include their ability to lower hyperglycaemia in animal models of type I, insulin-dependent diabetes mellitus (IDDM), and type II, non-insulin-dependent diabetes mellitus (NIDDM...
Several organo‐vanadium complexes (OVCs) have been shown to exert multiple insulino‐mimetic effects in rodent models of diabetes. We have shown that Bis(maltolato) OxoVanadium(IV) (BMOV) activates several components of the insulin signaling pathway such as phosphatidyl inositol‐3 kinase (PI3‐K) and protein kinase B (PKB). Forkhead Box Proteins (FOX...
A role of growth factor receptor transactivation and metalloproteinase in angiotensin II‐induced signaling events has been well established in vascular smooth muscle cells (VSMC). However, an involvement of receptor transactivation and metalloproteinase activation as upstream mediators of ET‐1‐induced signaling in VSMC has not been explored. In thi...
Vascular complications including impaired contractility and increased cell proliferation are the most common complications
associated with diabetes. Chronic hyperglycemia appears to be an important contributing factor in this process. Various signaling
pathways are implicated in diabetes/hyperglycemia-induced impaired vascular functions. Increased...
Vasoactive peptides, such as endothelin-1 (ET-1) and angiotensin II (AngII), are believed to contribute to the pathogenesis
of vascular abnormalities such as hypertension, atherosclerosis, hypertrophy, and restenosis. These peptides elicit their
biological effects through the activation of transmembrane guanine nucleotide-binding protein-coupled re...
Signal Transduction in Cardiovascular System in Health and Disease
Madhu B. Anand- Srivastava and Ashok K. Srivastava
This book has addressed the contributions of several key signal transduction pathways which are central to our understanding of cardiovascular physiology and pathophysiology. Aberrations in these signaling events have been suggest...
Nitric oxide (NO), in addition to its vasodilator action, has also been shown to antagonize the mitogenic and hypertrophic responses of growth factors and vasoactive peptides such as endothelin-1 (ET-1) in vascular smooth muscle cells (VSMCs). However, the mechanism by which NO exerts its antimitogenic and antihypertrophic effect remains unknown. T...
Transactivation of epidermal growth factor receptor (EGFR) is a well-documented mechanism by which vasoactive peptides and H2O2 elicit their cellular responses. However, a role for the insulin-like growth factor type-1 receptor (IGF-1R) transactivation in mediating the effects of angiotensin II (Ang II) and H2O2 in vascular smooth muscle cells from...
Excessive generation of reactive oxygen species (ROS) has been implicated in the pathogenesis of many diseases, including atherosclerosis, hypertension, and vascular complications of diabetes. However, the precise mechanisms by which ROS contribute to the development of these diseases are not fully characterized. Hydrogen peroxide (H2O2), a ROS, ha...
Endothelin-1 (ET-1), a vasoactive peptide, is believed to contribute to the pathogenesis of vascular abnormalities such as hypertension, atherosclerosis, hypertrophy and restenosis. ET-1 elicits its biological effects through the activation of two receptor subtypes, ET-A and ET-B that belong to a large family of transmembrane guanine nucleotide-bin...
Endothelin-1 (ET-1), a vasoactive peptide, is believed to contribute to the pathogenesis of vascular abnormali- ties such as hypertension, atherosclerosis, hypertrophy and restenosis. ET-1 elicits its biological effects through the activa- tion of two receptor subtypes, ET-A and ET-B that belong to a large family of transmembrane guanine nucleotide...
Vanadium(IV) oxo-bis(maltolato) (BMOV), an organovanadium compound, is a potent insulinomimetic agent and improves glucose homeostasis in various models of diabetes. We have shown previously that BMOV stimulates the phosphorylation of PKB which may contribute as one of the mechanisms for the insulinomimetic effect of this compound. However, the ups...
Evidence accumulated in recent years has revealed a potential role for reactive oxygen species (ROS) in the pathophysiology of cardiovascular diseases. However, the precise mechanisms by which ROS contribute to the development of these diseases are not fully established. Previous work from our laboratory has indicated that exogenous hydrogen peroxi...
Among several metals, vanadium has emerged as an extremely potent agent with insulin-like properties. These insulin-like properties have been demonstrated in isolated cells, tissues, different animal models of type I and type II diabetes as well as a limited number of human subjects. Vanadium treatment has been found to improve abnormalities of car...
Organo-vanadium compounds (OVC) have been shown to be more effective than inorganic vanadium compounds in ameliorating glucose homeostasis and insulin resistance in rodent models of diabetes mellitus. However, the precise molecular mechanism of OVC efficiency remains poorly defined. Since inorganic vanadium compounds have been found to activate sev...
Hydrogen peroxide (H2O2) mimics many physiological responses of insulin, and increased H2O2 generation via the Nox-4 subunit of NAD(P)H oxidase was recently demonstrated to serve as a critical early step in the insulin signaling pathway. Exogenously added H2O2 has also been shown to activate several key components of the insulin signaling cascade....
Inorganic and organic compounds of vanadium have been shown to exhibit a large range of insulinomimetic effects in the cardiovascular system, including stimulation of glucose transporter 4 (GLUT-4) translocation and glucose transport in adult cardiomyocytes. Furthermore, administration of vanadium compounds improves cardiac performance and smooth m...
Reactive oxygen species (ROS) have been shown to mediate the effects of several growth factors and vasoactive peptides, such as epidermal growth factor, platelet-derived growth factor, and angiotensin II (AII). Endothelin-1 (ET-1) is a vasoactive peptide which also exhibits mitogenic activity in vascular smooth muscle cells (VSMCs), and is believed...
We have shown earlier that extracellular signal-regulated kinases 1 and 2 (ERK1/2) and protein kinase B (PKB), two key mediators of growth-promoting and proliferative responses, are activated by hydrogen peroxide (H(2)O(2)) in A10 vascular smooth muscle cells (VSMC). In the present studies, using a series of pharmacological inhibitors, we explored...
This research explored the management devices followed in successful schools in the Indian context. In-depth case studies of three successful Navodaya schools were carried out. The schools were identified on the basis of the academic performance of students in the last three years in the national examinations and their participation in co-curricula...
Vanadium salts such as vanadyl sulfate (VS), potent inhibitors of protein tyrosine phosphatases, have been shown to mimic, augment, and prolong insulin's action. However, the molecular mechanism of responses to these salts is not clear. In the present studies, we examined if VS-induced effects on insulin action are associated with enhancement or au...
Oxidative stress has been implicated in the pathogenesis of a host of vascular abnormalities such as atherosclerosis, hypertension and in restenosis followed by balloon angioplasty. However, the molecular mechanism by which oxidative stress causes these abnormalities remains poorly characterized. Recent studies have shown that exposure of vascular...
Oxidative stress has been implicated in the pathogenesis of a host of vascular abnormalities such as atherosclerosis, hypertension
and in restenosis followed by balloon angioplasty. However, the molecular mechanism by which oxidative stress causes these
abnor-malities remains poorly characterized. Recent studies have shown that exposure of vascular...
It is well established that prolonged hyperglycemia may be a key contributor in the development of vascular complications in diabetes leading to vascular disease. An important feature of vascular disease is abnormal growth, proliferation, migration and hypertrophy of vascular smooth muscle cells (VSMC). However, the precise molecular events linking...
Type 1 and type 2 diabetic patients often show elevated plasma ketone body concentrations. Because ketone bodies compete with other energetic substrates and reduce their utilization, they could participate in the development of insulin resistance in the heart. We have examined the effect of elevated levels of ketone bodies on insulin action in prim...
Vascular dysfunction is among the most common complications associated with diabetes,1–3 and chronic hyperglycemia appears to be an important contributor in this process. 3 However, the precise mechanism(s) responsible for hyperglycemia-induced vascular dysfunction remain(s) poorly characterized.
Non-enzymatic glycation, enhanced production of diac...
Compounds of the trace element vanadium have been shown to mimic insulin in in vitro and in vivo systems. These compounds have been found to exert anti-diabetic effects in rodent models of type 1 and type 2 diabetes mellitus as well as in a limited number of studies in human diabetic subjects. Thus, vanadium compounds have emerged as agents for pot...
Insulin produces an influx of Ca(2+) into isolated rat hepatocyte couplets that is important to couple its tyrosine kinase receptor to MAPK activity (Benzeroual et al., Am. J. Physiol. 272, (1997) G1425-G1432. In the present study, we have examined the implication of Ca(2+) in the phosphorylation state of the insulin receptor (IR) beta-subunit and...
The possible roles of the mitogen-activated protein kinases (MAPKs) ERK-1 and ERK-2 in mediating growth-promoting and hypertrophic responses were investigated by examining the effect of H2O2 on ERK-1 and ERK-2 phosphorylation and activation in an established vascular smooth muscle cell (VSMC) line (A10). H2O2 treatment of VSMCs stimulated the phosp...
The mechanisms by which inorganic salts of the trace element vanadium mediate their insulinomimetic effects are not clearly understood and were investigated. We have shown previously that vanadium salts activate mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase activities (PI3-K) via a pathway that does not involve the insul...
Stimulation of glycogen synthesis is one of the major physiological responses modulated by insulin. Although, details of the precise mechanism by which insulin action on glycogen synthesis is mediated remains uncertain, significant advances have been made to understand several steps in this process. Most importantly, recent studies have focussed on...
Salts of the trace element vanadium, such as sodium orthovanadate and vanadyl sulfate (VS), exhibit a myriad of insulin-like effects, including stimulation of glycogen synthesis and improvement of glucose homeostasis in type I and type II animal models of diabetes mellitus. However, the cellular mechanism by which these effects are mediated remains...
The role of TNF-alpha in modulating intestinal crypt cell growth was examined, in comparison with EGF. Both significantly increased IEC-6 cell proliferation. Neither EGF nor TNF-alpha overcame the inhibitory effect on growth exerted by the tyrosine kinase inhibitor genistein. Immunoblots with phosphotyrosine antibodies showed increased tyrosine pho...
During the last 5 years several studies have documented an involvement of protein tyrosine kinases (PTKs) in smooth muscle contraction and Ca2+ mobilization. Most of these studies have utilized highly selective inhibitors of PTKs, genistein and tyrphostin and have shown that these inhibitors attenuated smooth muscle contraction induced by growth fa...
The present study was designed to investigate the presence of the fatty acid-binding protein (FABP(PM)) in the plasma membranes of skeletal muscles with different oxidative capacities for free fatty acid (FFA) oxidation during conditions of normal (fed) or increased (fasted) FFA utilization in the rat. Female Sprague-Dawley rats were either fed or...
The present study was undertaken to characterize the contractile effects of vanadate on thoracic aorta rings from virgin and term-pregnant rats. Vanadate caused concentration-dependent contraction in rat aortic rings with an EC50 (concentration producing 50% maximum response) of 0.10 mM. Contractions in response to vanadate were equivalent to the o...
Protein tyrosine phosphorylation is believed to play a central role in signaling pathways initiated by growth factor receptor activation. Recent studies have shown that various vasoactive peptides, in addition to eliciting a contractile response, also serve as growth factors for vascular smooth muscle ans stimulate tyrosyl phosphorylation of severa...
Effect of several vanadium salts, sodium orthovanadate, vanadyl sulfate and sodium metavanadate on protein tyrosine phosphorylation and serine/threonine kinases in chinese hamster ovary (CHO) cells overexpressing a normal human insulin receptor was examined. All the compounds stimulated protein tyrosine phosphorylation of two major proteins with mo...
1. Protein tyrosine kinase (PTK) activities were detected in both cytosolic and particulate fractions of cultured vascular smooth muscle cells by using poly (Glu: Tyr; 4:1) as an exogenous substrate. 2. The present distribution of the enzyme activity between these two fractions was 70 and 30 respectively. 3. The particulate and not the cytosolic en...
Treatment of Chinese hamster ovary (CHO) cells over-expressing the human insulin receptor (CHO-HIRc) with the insulin mimetic agent, vanadate, resulted in a dose- and time-dependent tyrosine phosphorylation of two proteins with apparent molecular sizes of 42 kDa (p42) and 44 kDa (p44). However, vanadate was unable to stimulate the tyrosyl phosphory...
Pentosan polysulfate, a polyanionic mucopolysaccharide, which has been shown to exert inhibitory effects on human immunodeficiency virus (HIV-I) replication, inhibited the activities of protein tyrosine kinases from lymphocytes (Jurkat cells) and rat lung in a concentration dependent manner. In addition, the autophosphorylation of p56lck, a lymphoc...
Protein tyrosine kinase (PTK) activities in methyl nitrosourea (MNU)-induced rat mammary carcinoma has been investigated by using poly (glu: tyr; 4:1) as an exogenous substrate. The PTK activity of the mammary carcinoma was almost equally distributed between the particulate and soluble (cytosolic) fractions at 110,000 X g. The activity of the parti...
The effects of purified Ca2+, phospholipid-dependent protein kinase (C-kinase) were studied on adenylate cyclase activity from rat brain striatum. C-kinase treatment of the membranes stimulated adenylate cyclase activity, the maximal stimulation between 50-80% was observed at 3.5 U/ml, whereas the catalytic subunit of cAMP dependent protein kinase...
By using poly(Glu: Tyr, 4:1) as an exogenous substrate, the characteristics of insulin receptor associated protein tyrosine kinase (PTK) from rabbit skeletal muscle has been compared with a growth factor-independent non-receptor PTK partially purified from rat lung particulate fraction. The two PTKs phosphorylated poly(Glu: Tyr; 4:1) very effective...
Incubation of a partially purified protein tyrosine kinase from rat lung with Mg2+ and ATP resulted in about 10-15-fold activation of the enzyme activity as judged by the phosphorylation of poly(Glu:Tyr,4:1), an exogenous substrate. The activation was time dependent and was associated with the phosphorylation of a single protein band of 50 kDa. Pho...
Quercetin, a naturally occurring bioflavonoid inhibited the activities of phosphorylase kinase and a partially purified tyrosine protein kinase from rat lung. The inhibition was rapid and concentration dependent. Quercetin at 100 microM inhibited the activities of phosphorylase kinase and tyrosine protein kinase by about 95 and 80-90 percent respec...
Adenylate cyclase activity was investigated in myocardial sarcolemma, aorta particulate fractions, and liver plasma membranes from control and 5-day streptozotocin-induced diabetic rats. The basal adenylate cyclase activity was increased in heart sarcolemma from diabetic rats, whereas the extent of stimulation by glucagon, dopamine, isoproterenol,...
Dimethyl sulfoxide (DMSO) stimulated the activity of a partially purified tyrosine protein kinase from rat lung. The stimulation was concentration dependent with a maximum stimulation (about 2 fold) observed at 10 per cent (V/V) DMSO. On the other hand, acetone (10 percent, V/V), did not exert any stimulatory effect on the enzyme activity. The stim...
Using the hindlimb perfusion system, we have studied glycogenolysis and glucose transport in resting and contracting skeletal muscle from normal and diabetic rats. Glucose transport was measured using the glucose analogue 2-deoxyglucose. The muscles were treated for 15 minutes with either saline solution, insulin (1 mU/mL) or epinephrine (10(-7) mo...