Short-period hypoxia increases mouse embryonic stem cell proliferation through cooperation of arachidonic acid and PI3K/Akt signalling pathways.

摘要: Hypoxia plays important roles in some early stages of mammalian embryonic development and various physiological functions. This study examined the effect arachidonic acid on short-period hypoxia-induced regulation G(1) phase cell-cycle progression inter-relationships among possible signalling molecules mouse stem cells. increased level hypoxia-inducible factor-1alpha (HIF-1alpha) expression H2O2 generation a time-dependent manner. In addition, hypoxia levels regulatory proteins (cyclin D(1), cyclin E, cyclin-dependent kinase 2 (CDK2) CDK4). Maximum increases these retinoblastoma phosphorylation were observed after 12-24 h exposure to hypoxic conditions, then decreased. Alternatively, CDK inhibitors, p21(Cip1) p27(Kip1) These results consistent with [3H]-thymidine incorporation cell counting. also [3H]-arachidonic release inhibition cPLA(2) reduced increase incorporation. The cyclooxygenase-2 (COX-2) was by COX-2 decreased Indeed, percentage cells S phase, cycle proteins, further conditions treatment compared normoxic conditions. Hypoxia-induced Akt mitogen-activated protein (MAPK) inhibited vitamin C (antioxidant, 10(-3) M). [(3)H]-thymidine attenuated LY294002 (PI3K inhibitor, 10(-6) M), inhibitor (10(-6) rapamycin (mTOR 10(-9) PD98059 (p44/42 10(-5) SB203580 (p38 MAPK Furthermore, [(3)H]-arachidonic blocked or SB203580, but not inhibitor. conclusion, up-regulates short time-period cyclins D(1) 4, through cooperation PI3K/Akt/mTOR, cPLA(2)-mediated signal pathways.