Novel Regulation of PKC-induced Inflammation by Akt and Protein Phosphatase 2A in Ovarian Granulosa Cells

Yen-Yu Lin ； David Sun ； Yuh-Lin Wu

《The Chinese Journal of Physiology》 63卷4期 (2020/08) Pp. 179-186

https://doi.org/10.4103/CJP.CJP_44_20

摘要

PKC-mediated inflammation is important in ovarian physiology. The roles of Akt and protein phosphatase 2A (PP2A) in PKC-mediated inflammation in ovarian granulosa cells (GCs) remain mostly unclear. PKC activator phorbol 12-myristate 13-acetate induced the Akt phosphorylation in rat primary GCs but reduced the Akt phosphorylation in KGN human GCs. In rat GCs, an inhibitory effect of PI3K inhibitor wortmannin and a stimulatory effect of Akt activator SC79 on PKC-induced cyclooxygenase-2 (COX-2)/PGE_2 production were noted; wortmannin and SC79 acted oppositely in human GCs. In rat GCs, PP2A inhibitor okadaic acid further enhanced the PKC-mediated promoter activation and elevation of mRNA and protein levels of the COX-2 gene, whereas PP2A activator sodium selenate attenuated the PKC-mediated COX-2 expression and promoter activation. PKC activation did not affect PP2A phosphorylation, but okadaic acid indeed augmented the PKC-induced NF-B nuclear translocation. Thus, PP2A appears to act as a negative modulator in PKC-mediated cellular inflammation in rat GCs, at least in part due to its attenuating effect on the PKC-induced NF-ĸB activation.

關鍵字

Akt ； granulosa cell ； phorbol 12-myristate 13-acetate ； protein phosphatase 2A

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