Impairment of Autophagic Flux Promotes Glucose Reperfusion-Induced Neuro2A Cell Death after Glucose Deprivation

Title
Impairment of Autophagic Flux Promotes Glucose Reperfusion-Induced Neuro2A Cell Death after Glucose Deprivation
Authors
손민
Issue Date
2013
Publisher
PLOS ONE
Series/Report no.
PLOS ONE ; Vol8 no.10 Startpage e76466 Endpage e76466
Abstract
Hypoglycemia-induced brain injury is a common and serious complication of intensive insulin therapy experienced by Type 1 diabetic patients. We previously reported that hypoglycemic neuronal death is triggered by glucose reperfusion after hypoglycemia rather than as a simple result of glucose deprivation. However, the precise mechanism of neuronal death initiated by glucose reperfusion is still unclear. Autophagy is a self-degradation process that acts through a lysosomemediated trafficking pathway to degrade and recycle intracellular components, thereby regulating metabolism and energy production. Recent studies suggest that autophagic and lysosomal dysfunction leads to abnormal protein degradation and deposition that may contribute to neuronal death. Here, we focused on the relationship between autophagy and lysosomal dysfunction in hypoglycemia-induced neuronal death. In neuronal cells, glucose reperfusion after glucose deprivation resulted in inhibition of autophagy, which may promote cell death. This cell death was accompanied with activation of caspase3 and the lysosomal proteases cathepsin B and D, which indicated impairment of autophagic flux. Taken together, these results suggest that interplay of autophagy, caspase3 activation and lysosomal proteases serve as a basis for neuronal death after hypoglycemia. Thus, we provide the molecular mechanism of neuronal death by glucose reperfusion and suggest some clues for therapeutic strategies to prevent hypoglycemia-induced neuronal death.
URI
http://dspace.inha.ac.kr/handle/10505/33281
ISSN
1932-6203
Appears in Collections:
Medical School/College of Medicine (의학전문대학원/의과대학) > Nursing (간호학) > Journal Papers, Reports(간호학 논문, 보고서)
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