Identification of the Protective Role of DJ‑1 in Hypoglycemic Astrocyte Injury Using Proteomics

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.