Protein Kinase C δ (PKCδ) Splice Variants Modulate Apoptosis Pathway in 3T3L1 Cells during Adipogenesis

• Published in: The Journal of biological chemistry Vol. 288; no. 37; pp. 26834 - 26846
• Main Authors: Patel, Rekha, Apostolatos, André, Carter, Gay, Ajmo, Joanne, Gali, Meghanath, Cooper, Denise R., You, Min, Bisht, Kirpal S., Patel, Niketa A.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 13.09.2013
• Subjects: Adipogenesis; Alternative Splicing; Obesity; Protein Kinase C (PKC); Resveratrol; Obesity; Alternative Splicing; Protein Kinase C (PKC); Resveratrol; Adipogenesis
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M113.482638

Increased food intake and lack of physical activity results in excess energy stored in adipocytes, and this imbalance contributes to obesity. New adipocytes are required for storage of energy in the white adipose tissue. This process of adipogenesis is widely studied in differentiating 3T3L1 preadipocytes in vitro. We have identified a key signaling kinase, protein kinase C delta (PKCδ), whose alternative splice variant expression is modulated during adipogenesis. We demonstrate that PKCδII splice variant promotes survival in differentiating 3T3L1 cells through the Bcl2 pathway. Here we demonstrate that resveratrol, a naturally occurring polyphenol, increases apoptosis and inhibits adipogenesis along with disruption of PKCδ alternative splicing during 3T3L1 differentiation. Importantly, we have identified a PKCδII splice variant inhibitor. This inhibitor may be a valuable tool with therapeutic implications in obesity. Background: Differentiation of preadipocytes into mature adipocytes (adipogenesis) is widely studied in vitro in mouse 3T3L1 cells. Results: Expression pattern of PKCδ alternatively spliced variants switches during adipogenesis in 3T3L1 cells. Conclusion: PKCδII promotes adipocyte survival via Bcl2 pathway. SEAM is a novel PKCδII inhibitor. Significance: Regulation of PKCδ splice variants in adipocytes may have therapeutic implications for obesity.