Stimulation of multiple mitogen-activated protein kinase sub-families by oxidative stress and phosphorylation of the small heat shock protein, HSP25/27, in neonatal ventricular myocytes

摘要: We investigated the activation of three subfamilies mitogen-activated protein kinases (MAPKs), namely stress-activated kinases/c-Jun N-terminal (SAPKs/JNKs), extracellularly responsive (ERKs) and p38-MAPK, by oxidative stress as exemplified H2O2 in primary cultures neonatal rat ventricular myocytes. The 46 54 kDa species SAPKs/JNKs were activated 5- 10-fold, respectively, 0.1 mM (the maximally effective concentration). Maximal occurred at 15-30 min, but was still detectable after 2 h. Both ERK1 ERK2 16-fold with a similar time course to SAPKs/JNKs, this comparable their 1 microM PMA, most powerful activator ERKs that we have so far identified these cells. inhibited PD98059, which inhibits MAPK (or ERK) kinases, kinase C (PKC) inhibitor, GF109203X. ERK also down-regulation PMA-sensitive PKC isoforms. p38-MAPK shown an increase its phosphorylation. However, maximal phosphorylation (activation) more rapid (<5 min) than for or ERKs. studied downstream consequences examining MAPK-activated (MAPKAPK2) MAPKAPK2 substrate, small heat shock HSP25/27. As rapidly (maximal within 5 H2O2. This abolished 10 SB203580, selective inhibitor certain HSP25/27 followed SB203580. Phosphorylation associated decrease aggregation state. These data indicate is all Activation MAPKs has been development hypertrophic phenotype. stimulation consequent may be important cardioprotection.