As a common complication of glycemic control in patients with diabetes, hypoglycemia often leads to brain dysfunction or damage. To identify new mechanisms underlying hypoglycemic brain injury, we determined the difference of protein expression profiles in brains between hypoglycemic rats and sham hypoglycemic controls by isobaric tags for relative and absolute quantitation (iTRAQ) analysis. Among the 89 deregulated proteins, DJ-1 protein (Park7) was verified to be upregulated following hypoglycemia insult in vivo and glucose deprivation in an astrocyte cell line (CTX-TNA2) cultured in vitro. Further studies indicated the pro-survival role of autophagy activation and impaired autophagy flux in CTX-TNA2 cells short of glucose. DJ-1 knockdown hindered the initiation of the autophagy process via the AMPK/mTOR pathway and aggravated cell death induced by glucose deficiency. Taken together, our results show that responsive overexpression of DJ-1 plays a protective role against hypoglycemic astrocyte injury partly mediated by the regulation of autophagy.
Keywords: DJ-1; autophagy; brain injury; hypoglycemia; iTRAQ.