title: Protein kinase C δ (PKCδ) splice variants modulate apoptosis pathway in 3T3L1 cells during adipogenesis: identification of PKCδII inhibitor.
abstract: 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.
authors.affiliation: From the James A Haley Veterans Hospital, Tampa, Florida 33612 and.
authors.forename: Rekha
authors.initials: R
authors.lastname: Patel
authors.forename: André
authors.initials: A
authors.lastname: Apostolatos
authors.forename: Gay
authors.initials: G
authors.lastname: Carter
authors.forename: Joanne
authors.initials: J
authors.lastname: Ajmo
authors.forename: Meghanath
authors.initials: M
authors.lastname: Gali
authors.forename: Denise R
authors.initials: DR
authors.lastname: Cooper
authors.forename: Min
authors.initials: M
authors.lastname: You
authors.forename: Kirpal S
authors.initials: KS
authors.lastname: Bisht
authors.forename: Niketa A
authors.initials: NA
authors.lastname: Patel
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis; D017398:Alternative Splicing; D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D059808:Polyphenols / Q000737:chemistry; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors* / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry*; D014162:Transfection
chemical_list: D059808:Polyphenols; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D013267:Stilbenes; D051745:Protein Kinase C-delta; D000077185:Resveratrol
keywords: Adipogenesis; Alternative Splicing; Obesity; Protein Kinase C (PKC); Resveratrol
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