Activation of c-Jun N-terminal kinase is essential for oxidative stress-induced Jurkat cell apoptosis by monochloramine
Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata, Okayama 700-8558, Japan. Leukemia Research
(Impact Factor: 2.35).
09/2008; 33(1):151-8. DOI: 10.1016/j.leukres.2008.07.009
Leukemic cell apoptosis may be enhanced by appropriate oxidative stress. We report here the mechanism of Jurkat cell apoptosis by monochloramine (NH(2)Cl), a neutrophil-derived oxidant. NH(2)Cl induced caspase-dependent apoptosis, which was preceded by cytochrome c and Smac/Diablo release from mitochondria. Within 10min of NH(2)Cl treatment, c-Jun N-terminal kinase (JNK) activation and elevation of cytosolic Ca(2+) were observed. JNK inhibitors (SP600125 or JNK inhibitor VIII) significantly suppressed the apoptosis as well as caspase cleavage and cytochrome c release. In contrast, Ca(2+) chelation by EGTA+acetoxymethyl-EGTA had no effects on apoptosis. Our results indicated that JNK activation contributed most importantly to the NH(2)Cl-induced apoptosis.
Available from: Nosratola D Vaziri
- "Spermine-mediated apoptosis triggered by oxidative stress has also been demonstrated in a variety of cell systems, including ischaemia-induced apoptosis of cardiac myoblasts (Maccarrone et al., 2001; Takano et al., 2005; Tantini et al., 2006). Emerging evidence now suggests that oxidative stress can promote JNK activation (Osto et al., 2008; Wei et al., 2008; Ogino et al., 2009), which constitutes a critical component of apoptotic signalling in various cells, including muscle cells (Tamagno et al., 2003; Sinha- Hikim et al., 2007; Braga et al., 2008; Philpott and Facci, 2008; Nadeau et al., 2009). Thus, the signal for JNK activation most likely emanates from spermine-induced generation of oxidative stress. "
[Show abstract] [Hide abstract]
ABSTRACT: CKD (chronic kidney disease) is a public health problem, mediated by haemodynamic and non-haemodynamic events including oxidative stress. We investigated the effect of two GSH (glutathione) precursors, NAC (N-acetylcysteine) and cystine as the physiological carrier of cysteine in GSH with added selenomethionine (F1) in preventing spermine (uraemic toxin)-induced apoptosis in cultured human aortic VSMC (vascular smooth muscle cells). VSMCs exposed to spermine (15 microM) with or without antioxidants (doses 50, 100, 200 and 500 microg/ml) were assessed for apoptosis, JNK (c-Jun-NH2-terminal kinase) activation and iNOS (inducible nitric oxide synthase) induction and activation of intrinsic pathway signalling. Spermine exposure resulted in activation of JNK and iNOS induction and apoptosis. NAC and F1 (dose range 50-500 microg/ml) attenuated spermine-induced acceleration of VSMC apoptosis but only F1 (at 200 and 500 microg/ml) maintained spermine-induced apoptosis at control levels. Spermine-induced JNK activation was prevented by 200 microg/ml of both NAC and F1, while iNOS induction was blocked only by F1. Notably, the adverse effects of spermine on BAX/BCL-2 ratio, cytochrome c release and caspase activation was fully attenuated by F1. In conclusion, F1 was more effective than NAC in preventing spermine-induced apoptosis and downstream changes in related signal transduction pathways in VSMCs. Further studies are needed to examine the effect of these compounds in preventing CKD-associated vascular disease.
Available from: Cédric Chaveroux
[Show abstract] [Hide abstract]
ABSTRACT: It has been well established that amino acid availability can control gene expression. Previous studies have shown that amino
acid depletion induces transcription of the ATF3 (activation transcription factor 3) gene through an amino acid response element (AARE) located in its promoter. This event
requires phosphorylation of activating transcription factor 2 (ATF2), a constitutive AARE-bound factor. To identify the signaling
cascade leading to phosphorylation of ATF2 in response to amino acid starvation, we used an individual gene knockdown approach
by small interfering RNA transfection. We identified the mitogen-activated protein kinase (MAPK) module MEKK1/MKK7/JNK2 as
the pathway responsible for ATF2 phosphorylation on the threonine 69 (Thr69) and Thr71 residues. Then, we progressed backwards
up the signal transduction pathway and showed that the GTPase Rac1/Cdc42 and the protein Gα12 control the MAPK module, ATF2
phosphorylation, and AARE-dependent transcription. Taken together, our data reveal a new signaling pathway activated by amino
acid starvation leading to ATF2 phosphorylation and subsequently positively affecting the transcription of amino acid-regulated
Available from: Jörg Flemmig
[Show abstract] [Hide abstract]
ABSTRACT: Polymorphonuclear leukocytes (PMNs) are important players in innate and acquired immunity. These cells accumulate at inflammatory sites and contribute to host defence, regulation of the inflammatory process, and also to tissue injury. One of the key components of PMNs is the heme-containing enzyme myeloperoxidase (MPO) that is stored in large amount in azurophilic granules of resting cells. Here we review the (patho)physiological role of MPO from the viewpoint of participation of PMNs in immune reactions. Myeloperoxidase is able to catalyse a wide range of one- and two-electron substrate oxidations. With special products, MPO contributes to apoptosis induction in PMNs and other cells, and, thus, to termination of inflammatory response. On the other hand, MPO released from necrotic cells promotes an inflammation by further recruitment of PMNs, and chemical modification of proteins and other tissue constituents. Myeloperoxidase is a fascinating, multifunctional, and challenging enzyme that has not yet revealed all its secrets.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.