PMID- 17980966 OWN - NLM STAT- MEDLINE DCOM- 20080321 LR - 20211203 IS - 0304-3940 (Print) IS - 0304-3940 (Linking) VI - 429 IP - 1 DP - 2007 Dec 11 TI - Insulin rescues ES cell-derived neural progenitor cells from apoptosis by differential regulation of Akt and ERK pathways. PG - 49-54 AB - Transplantation of embryonic stem (ES) cell-derived neural progenitor cells (ES-NPCs) is one promising technology for the treatment of spinal cord injury. Promoting ES-NPC survival at the lesion site is critical for the successful treatment. We tested the role of insulin in promoting mouse ES-NPC survival. Cultured ES-NPCs survived when maintained in normoxia but underwent apoptosis when exposed to hypoxia. Insulin rescued ES-NPCs from hypoxia-induced cell death. This effect could be blocked by the phosphatidylinositol 3-kinase (PI3K)/Akt pathway inhibitor LY294002. In contrast, mitogen-activated protein kinase (MAP)/extracellular-signal-regulated kinase (ERK) pathway inhibitor U0126 potentiated insulin-mediated survival. Immunoblots revealed that insulin upregulated activation of Akt and inhibited ERK activation through the PI3K pathway. In addition, we showed that insulin reduced the activation of caspase-3, the key executor of apoptosis. In summary, our data suggest that insulin prevent apoptosis in ES-NPCs by activating Akt and inhibiting ERK through the PI3K pathway. FAU - Zhao, Yanhong AU - Zhao Y AD - Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, 3 Nanyitiao, Zhongguancun, Beijing 100080, People's Republic of China. FAU - Xiao, Zhifeng AU - Xiao Z FAU - Gao, Yuan AU - Gao Y FAU - Chen, Bing AU - Chen B FAU - Zhao, Yannan AU - Zhao Y FAU - Zhang, Jing AU - Zhang J FAU - Dai, Jianwu AU - Dai J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20071012 PL - Ireland TA - Neurosci Lett JT - Neuroscience letters JID - 7600130 RN - 0 (Butadienes) RN - 0 (Chromones) RN - 0 (Enzyme Inhibitors) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 0 (Morpholines) RN - 0 (Nerve Tissue Proteins) RN - 0 (Nitriles) RN - 0 (U 0126) RN - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) RN - EC 2.7.11.1 (Oncogene Protein v-akt) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Animals MH - Apoptosis/*drug effects MH - Butadienes/pharmacology MH - Cell Differentiation/*drug effects MH - Cells, Cultured MH - Chromones/pharmacology MH - Drug Interactions MH - Embryo, Mammalian MH - Embryonic Stem Cells MH - Enzyme Inhibitors/pharmacology MH - Extracellular Signal-Regulated MAP Kinases MH - Gene Expression Regulation/drug effects MH - Hypoglycemic Agents/*pharmacology MH - Hypoxia/drug therapy/physiopathology MH - Insulin/*pharmacology MH - Mice MH - Morpholines/pharmacology MH - Nerve Tissue Proteins/metabolism MH - Neurons/*drug effects MH - Nitriles/pharmacology MH - Oncogene Protein v-akt MH - Protein Serine-Threonine Kinases/*physiology MH - Signal Transduction/drug effects EDAT- 2007/11/06 09:00 MHDA- 2008/03/22 09:00 CRDT- 2007/11/06 09:00 PHST- 2007/08/09 00:00 [received] PHST- 2007/09/28 00:00 [revised] PHST- 2007/09/30 00:00 [accepted] PHST- 2007/11/06 09:00 [pubmed] PHST- 2008/03/22 09:00 [medline] PHST- 2007/11/06 09:00 [entrez] AID - S0304-3940(07)01071-3 [pii] AID - 10.1016/j.neulet.2007.09.076 [doi] PST - ppublish SO - Neurosci Lett. 2007 Dec 11;429(1):49-54. doi: 10.1016/j.neulet.2007.09.076. Epub 2007 Oct 12.