Novel regulation of PKC-induced inflammation by Akt and protein phosphatase 2A in ovarian granulosa cells

• Main Authors: Yen-Yu Lin, David Sun, Yuh-Lin Wu
• Format: Article
• Language: English
• Published: Wolters Kluwer Medknow Publications 2020-01-01
• Series: Chinese Journal of Physiology
• Subjects: akt; granulosa cell; phorbol 12-myristate 13-acetate; protein phosphatase 2a
• Online Access: http://www.cjphysiology.org/article.asp?issn=0304-4920;year=2020;volume=63;issue=4;spage=179;epage=186;aulast=Lin
• ISSN: 0304-4920; 2666-0059

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)/PGE2production 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-κB 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-κB activation.