Mild hypoxia promotes survival and proliferation of SOD2-deficient astrocytes via c-Myc activation.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Jing LiuPak H Chan

Abstract

Mouse astrocytes deficient in the mitochondrial form of manganese superoxide dismutase (SOD2) do not survive in culture under atmospheric air with 20% oxygen (O2), which is a common condition for cell cultures. Seeding the cells and maintaining them under mild hypoxic conditions (5% O2) circumvents this problem and allows the cells to grow and become confluent. Previous studies from our laboratory showed that this adaptation of the cells was not attributable to compensation by other enzymes of the antioxidant defense system. We hypothesized that transcriptional activity and upregulation of genes other than those with an antioxidant function are involved. Our present study shows that c-Myc was significantly induced and that it inhibited p21 and induced proteins such as cyclin-dependent kinases, cyclin D, and cyclin E, which are involved in the cell cycle process, along with phosphorylation of the retinoblastoma protein and Cdc2 (cell division cycle 2). These mechanisms contribute to cell proliferation. Small interfering RNA of c-Myc, however, blocked proliferation of SOD2 homozygous (SOD2-/-) astrocytes under mild hypoxia consisting of 5% O2, whereas it did not affect the growth of wild-type astrocytes. Our results indicate that...Continue Reading

Citations

Apr 24, 2010·BMC Cancer·Kara C SedorisDonald M Miller
Dec 17, 2014·Biochimica Et Biophysica Acta·Licht MiyamotoKoichiro Tsuchiya
Dec 15, 2015·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Takuma WakaiPak H Chan
Mar 9, 2017·International Journal of Environmental Research and Public Health·Ming XuBaoli Zhu
Nov 25, 2021·American Journal of Physiology. Cell Physiology·Gregory G VandenbergAngela L Scott

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