Downregulation of long noncoding RNA H19 rescues hippocampal neurons from apoptosis and oxidative stress by inhibiting IGF2 methylation in mice with streptozotocin-induced diabetes mellitus.
The diabetes mellitus (DM)-induced reduction of neurogenesis in the hippocampus is consequently accompanied by cognitive decline. The present study set out to define the critical role played by long noncoding RNA H19 (lncRNA H19) in the apoptosis of hippocampal neurons, as well as oxidative stress (OS) in streptozotocin (STZ)-induced DM mice through regulation of insulin-like growth factor 2 (IGF2) methylation. The expression of lncRNA H19 in the hippocampal neurons and surviving neurons were detected. Hippocampal neurons were cultured and transfected with oe-H19, sh-H19, oe-IGF2, or sh-IGF2, followed by detection of the expressions of IGF2 and apoptosis-related genes. Determination of the lipid peroxide and glutathione levels was conducted, while antioxidant enzyme activity was identified. The IGF2 methylation, the binding of lncRNA H19 to DNA methyltransferase, and the binding of lncRNA H19 to IGF2 promoter region were detected. DM mice exhibited high expressions of H19, as well as a decreased hippocampal neurons survival rate. Higher lncRNA H19 expression was found in DM. Upregulated lncRNA H19 significantly increased the expression of Bax and caspase-3 but decreased that of Bcl-2, thus promoting the apoptosis of hippocampal neuron. Besides, upregulation of lncRNA H19 induced OS. LncRNA H19 was observed to bind specifically to the IGF2 gene promoter region and promote IGF2 methylation by enriching DNA methyltransferase, thereby silencing IGF2 expression. Taken together, downregulated lncRNA H19 reduces IGF2 methylation and enhances its expression, thereby suppressing hippocampal neuron apoptosis and OS in STZ-induced (DM) mice.
['Yu|Jin-Lu|JL|', 'Li|Chao|C|', 'Che|Li-He|LH|', 'Zhao|Yu-Hao|YH|', 'Guo|Yun-Bao|YB|0000-0002-5666-7344']
D000818:Animals D017209:Apoptosis D019175:DNA Methylation D003920:Diabetes Mellitus D003921:Diabetes Mellitus, Experimental D005786:Gene Expression Regulation D018392:Genomic Imprinting D006624:Hippocampus D006801:Humans D007335:Insulin-Like Growth Factor II D008780:Methyltransferases D051379:Mice D009474:Neurons D018384:Oxidative Stress D011401:Promoter Regions, Genetic D019253:Proto-Oncogene Proteins c-bcl-2 D062085:RNA, Long Noncoding D051028:bcl-2-Associated X Protein
long noncoding RNA H19 hippocampal neuron apoptosis oxidative stress methylation streptozotocin-induced diabetes mellitus insulin-like growth factor 2