熱ショックによるインスリン受容体自己リン酸化抑制の機序

概要

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Effects of heat shock on insulin signal transduction were examined using rat hepatoma H4EII(H4) cells. Exposure of cells to 45℃ for 10 min moderately activated ERK (Extracellular signal-regulated protein kinase), whereas strongly inhinbit insulin-stimulated ERK activation and insulin-stimulated autophosphorylation of the insulin receptor. The response to insulin were partially restored at 4h of the incubation at 37℃ after heat shock. Number of insulin receptors on the surface of H4 cells gradually decreased after heat shock and become 50% of the control cells at 4h of the incubation at 37℃ after heat shock. The inhibition of insulin-stimulated ERK activation was well correlated with a defect of autophosphorylation of the insulin receptor, but not with the decrease in the receptor number. Heat shock did not interfered with PMA (phorbol 12-myristate 13-acetate)-stimulated ERK activation. Increased intracellular cAMP concentration inhibits heat shock-induced ERK activation, but had no effects on heat shocked decrease in insulin-stimulated autophosphorylation of the insulin receptor. These results show that heat shock directly interferes with insulin signaling through the inhibition of autophosphorylation of the insulin receptor at the postbinding level.
山口県立大学の論文
2006-03-25