P38 MAPK activity

Sun Y, Cheng Z, Ma L, Pei G. Beta-arrestin2 is critically involved in CXCR4-mediated chemotaxis, and this is mediated by its enhancement of p38 MAPK activation. J Biol Chem 2002 277(51) 49212 19219. 

Roux, P. P., and Blenis, J. (2004). ERK and p38 MAPK-activated protein kinases A family of protein kinases with diverse biological functions. Microbiol. Mol. Biol. Rev. 68, 320-344. 

Previous studies have reported that ERKs are characteristically associated with cell proliferation and protection from apoptosis (Bl, XI), while activation of JNK and p38 MAPK can promote apoptosis in many systems, including B lymphocytes (G5), cerebellar granule cells (K3), hematopoietic cells (K8), and neuronal cells (M3, XI). On the other hand, a recent report found that a pyridinyl imidazole, SB 202190, the specific inhibitor of p38 MAPK, by itself was sufficient to induce apoptosis in T lymphocyte Jurkat cells (N2). Moreover, Th-2-derived cytokine IL-5, the ERK activator and antiapoptotic factor for eosinophils, could also activate p38 MAPK in human eosinophils (BIO). We recently reported that cytokine IL-3, IL-5, and GM-CSF could prolong survival of human eosinophilic leukemic (EoL-1) cells through the transient activation of ERK (W15). On the other hand, activation of p38 MAPK in EoL-1 cells by the NSAID sodium salicylate (NaSal) could lead to apoptosis (W15). We also found that the suppression of ERK using ERK antisense phosphorothioate oligodeoxynucleotides could promote the apoptosis of peripheral blood eosinophils (W16). Moreover, we found that dexamethasone-induced apoptosis and activation of JNK and p38 MAPK activity in eosinophils are regulated by caspases (Z2). 

Bazuine M, Ouwens DM Gomes de Mesquita DS, Maassen JA. 2003. Arsenite stimulated glucose transport in 3T3-L1 adipocytes involves both Glut4 translocation and p38 MAPK activity. Eur J Biochem 270 3891-3903. 

Marais, E., Genade, S., Huisamen, B., Strijdom, J.G., Moolman, J.A., and Lochner, A. 2001b. Activation of p38 MAPK induced by a multi-cycle ischaemic preconditioning protocol is associated with attenuated p38 MAPK activity during sustained ischaemia and reperfusion. J. Mol. Cell. Cardiol. 33 769-778. 

S. Sanada, M. Kitakaze, P.J. Papst, K. Hatanaka, H. Asanuma, T. Aki,Y. Shinizaki, H. Ogita, K. Node, S. Takashima, M. Asakura, T. Yamada, T. Fukushima, A. Ogai, T. Kuzuya, H. Mori, N. Terada, K. Yoshida and M. Hori, Role of phasic dynamism of p38 MAPK activation in ischemic preconditioning of canine heart, Circ. Res. 88, 175-180 (2001). 

Estrogens induced cardioprotection seems to involve the ERa receptor. In fact, hearts from estrogens receptor-alpha knock out mice were sensitive to ischemia and reperfusion injury". Furthermore, estrogens receptor modulators which lack some of the estrogens side effects are shown to be cardioprotective raloxifene limited infarct size and incidence of ventricular fibrillation in an in vivo canine model of coronary occlusion and reperfusion. This effect was attenuated by the inhibition of NO synthase (NOS) or calcium activated potassium channels and completely abolished by both blocking NOS and Ca2+-activated K+ channels. Ischemia and reperfusion induced p38 MAPK activation was also attenuated in raloxifene treated hearts.12... 

A detrimental effect caused by androgens is also reported. Blockade of the endogenous testosterone by flutamide or depletion of testosterone (castration) improved myocardial function of the perfused rat hearts subjected to ischemia and reperfusion. This response was associated with decreased caspase l, caspase-3, caspase-11, decreased TNF-alpha, IL-1 beta, IL-6, decreased ischemia and reperfusion induced p38 MAPK activation and increased Bcl-2 expression in castrated and flutamide treated males.15 Accordingly, supraphysiological doses of nandrolone taken during exercise or under sedentary conditions increased myocardial susceptibility to ischemia and reperfusion injury in perfused rat hearts. Pre-ischemic c-AMP concentrations and pre-ischemic and reperfusion TNF-alpha concentrations were found to be increased in those hearts.16... 

Nth-terminal kinase (JNK) and p38 MAPK activity in eosinophils is regulated by caspases. Interestingly, the caspases involved are not the common apoptosis-related caspase-3 or -8, as is the case in other cells. The elucidation of the role of caspases in eosinophil apoptosis may thus facilitate the development of more specific and effective treatments for this type of allergic inflammation [69]. 

Ji RR, Samad TA, Jin SX, et al. (2002) p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPVl levels and maintains heat hyperalgesia. Neuron 36 57-68 Jia Y, Lee LY (2007) Role of TRPV receptors in respiratory diseases. Biochim Biophys Acta 1772 915-927... 

Tanaka T, Ueno M, Yamashita T (2009) Engulfment of axon debris by microglia requires p38 MAPK activity. J Biol Chem 284 21626-21636... 

Eom HJ, Choi J (2010) p38 MAPK activation, DNA damage, cell cycle arrest and apoptosis as mechanisms of toxicity of silver nanoparticles in Jurkat T cells. Environ Sci Technol 44(21) 8337-8342... 

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