Autophagy impairment mediated by S-nitrosation of ATG4B leads to neurotoxicity in response to hyperglycemia.

ABSTRACT: The majority of diabetic patients develop neuropathy and there is an increasing prevalence of neurodegeneration in the central nervous system (CNS). However, the mechanism behind this is poorly understood. Here we first observed that macroautophagy/autophagy was suppressed in the hippocampus of diabetic GK rats with hyperglycemia, whereas it was unchanged in ob/ob mice without hyperglycemia. Autophagy could be directly inhibited by high glucose in mouse primary hippocampal neurons. Moreover, autophagy was protective in high-glucose-induced neurotoxicity. Further studies revealed that autophagic flux was suppressed by high glucose due to impaired autophagosome synthesis illustrated by mRFP-GFP-LC3 puncta analysis. We showed that decreased autophagy was dependent on NO produced under high gl

SUBMITTER: Li Y 

PROVIDER: S-EPMC5529069 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature