Insulin rescues ES cell-derived neural progenitor cells from apoptosis by differential regulation of Akt and ERK pathways.
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.
Zhao
Yanhong
Y
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.
Xiao
Zhifeng
Z
Gao
Yuan
Y
Chen
Bing
B
Zhao
Yannan
Y
Zhang
Jing
J
Dai
Jianwu
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002070:Butadienes / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004347:Drug Interactions; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases; D005786:Gene Expression Regulation / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D000860:Hypoxia / Q000188:drug therapy / Q000503:physiopathology; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D009570:Nitriles / Q000494:pharmacology; D051058:Oncogene Protein v-akt; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects
D002070:Butadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D009025:Morpholines; D009419:Nerve Tissue Proteins; D009570:Nitriles; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051058:Oncogene Protein v-akt; D017346:Protein Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases