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We studied the possible role of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase 1/2 (JNK1/2) and p38 in response to hypoxia in heart of streptozotocin (STZ)-induced diabetic rats. Rats were divided into three groups: controls (Group 1), control+hypoxia (Group 2), and diabetes mellitus (Group 3). Hypoxia was applied by placing the animals in a normobaric hypoxia chamber with a gas mixture of 10 % O(2) and 90 % N(2) for 30 minutes. Compared with controls, diabetic rats showed higher plasma glucose levels. Diabetes significantly increased the mitogen-activated protein kinase (MAPK) phosphorylation. Diabetic hearts showed higher TUNEL-positive cells, MDA levels and lactate dehydrogenase (LDH) release in the culture media than control rats. Under normoxia, diabetic hearts showed lower p38 activation than controls. However, hypoxia increased p38 phosphorylation in hearts of control and diabetic rats, but only in diabetic rats its phosphorylation was higher than normoxic controls. Our data show that MAPK phosphorylation in diabetic rat heart is differentially regulated by hypoxia and may be related to reactive oxygen species-induced apoptosis in the heart. work of any sponsoring or financing entity.
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