| Summary: | 碩士 === 慈濟大學 === 生理暨解剖醫學碩士班 === 102 === Intermittent hypoxia (IH) plays a critical role in sleep breathing disorder-associated hippocampus impairments, including neurocognitive deficits, irreversible memory and learning impairments. IH-induced neuronal injury in the hippocampus may result from reduced precursor cell proliferation and decrease the numbers of postmitotic differentiated neurons. ERK pathway is an important pathway to mediated cell proliferation or cell differentiation, which can be inhibited by protein phosphatase 2A (PP2A). However, the mechanisms underlying IH-induced reactive oxygen species (ROS) generation effects on cell proliferation and neuronal differentiation remain largely unknown.
We used Pheochromocytoma cell (PC12) to find the cell proliferation and differentiation change after IH treatment for 1－4 days. Also to determine the mechanisms change between the ROS, PP2A and ERK pathway. In the results, we found ROS generation significantly increased after 1–4 days of IH without increased cell death, which resulted in increased PP2A mRNA and protein levels. After 3–4 days of IH, ERK1/2 protein phosphorylation decreased, which could be reversed by superoxide dismutase (SOD), 1,10-phenanthroline (Phe), the PP2A phosphorylation inhibitors, okadaic acid (OKA) and cantharidin, and the ERK phosphorylation activator nicotine. In particular, the significantly reduced cell proliferation and increased proportions of cells in the G0/G1 phase after 1–4 days of IH, resulted in decreased numbers of PC12 cells. In addition, the numbers of NGF-induced PC12 cells with neurite outgrowths after 3–4 days of IH were less than those after 4 days of RA, which was also reversed by SOD, Phe, PP2A inhibitors and an ERK activator.
Our results suggest that intermittent hypoxia increased ROS generation and PP2A protein levels. It also decreased ERK pathway activation, which inhibited PC12 cell proliferation and NGF-induced differentiation.
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