PPARgamma-mediated advanced glycation end products regulation of neural stem cells.
Hyperglycemia is accompanied by an accelerated rate of advanced glycation end products (AGEs) formation, which is found to be associated with the pathogenesis of diabetic cognitive deficit, including Alzheimer's disease (AD). Peroxisome proliferator-activated receptor gamma (PPARgamma) plays an important role in controlling the proliferation of neural stem cells (NSCs) and their neuronal differentiation. We investigate the hypothesis that PPARgamma could mediate AGEs-related regulation of NSCs, by which AGEs possibly fulfill important roles in diabetic-related cognitive impairment. We found that AGEs down-regulated the proliferation and neurogenic differentiation of NSCs, and protein level of PPARgamma. PPARgamma agonist reversed the proliferation through the aid of AGE-BSA, with the exclusion of the neuronal differentiation of the NSCs which were also downregulated by AGE-BSA. These findings extend our understanding of the central role of PPARgamma in AGEs-related neurogenesis impairment, which probably increased risks of cognitive deficits or AD in diabetic patients.
Wang
Shao-hua
SH
Department of Endocrinology, affiliated ZhongDa Hospital of Southeast University, Nanjing, PR China. wshgyj@yahoo.com.cn
Sun
Zi-lin
ZL
Guo
Yi-jing
YJ
Yuan
Yang
Y
Li
Ling
L
D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism*; D051381:Rats; D000077154:Rosiglitazone; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology
D017127:Glycation End Products, Advanced; D047495:PPAR gamma; D045162:Thiazolidinediones; C081628:advanced glycation end products-bovine serum albumin; D000077154:Rosiglitazone; D012710:Serum Albumin, Bovine; D053148:Caspase 3