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

Abstract

Background: Differentiation of preadipocytes into mature adipocytes (adipogenesis) is widely studied in vitro in mouse 3T3L1 cells. Results: Expression pattern of PKC␦ alternatively spliced variants switches during adipogenesis in 3T3L1 cells. Conclusion: PKC␦II promotes adipocyte survival via Bcl2 pathway. SEAM is a novel PKC␦II inhibitor. Significance: Regulation of PKC␦ splice variants in adipocytes may have therapeutic implications for obesity.

PKCδ regulates hepatic triglyceride accumulation and insulin signaling in Leprdb/db mice

“…In agreement with this conclusion, PKCd has been reported to be activated in adipocytes isolated from high fat fed mice [17,18]. Further, a splice variant of PKCd is differentially regulated during adipogenesis and promotes adipocyte cell survival [19,20].…”

Resveratrol enhances splicing of insulin receptor exon 11 in myotonic dystrophy type 1 fibroblasts

“…RES has been reported to affect many major biological processes [26,27]. The influence of RES on splicing has been studied in the alternative splicing of the SRp20, SMN2, and protein kinase C delta pre-mRNAs [14,28] and the splicing activity of TNF-alpha premRNA [29]. Recently, RES was shown to reverse abnormal splicing caused by a mutation in the GAA gene and was proposed as a molecule to treat glycogen storage disease type II [10].…”

Polyphenol compounds and PKC signaling

“…Recent studies show that resveratrol's neuroprotective effects are mediated by the activation of PKCγ at 3 μM [133] and anti-neutrophil activity by inhibiting PKC activity at 10 and 100 μM [134]. Resveratrol regulates cellular PKCα and PKCδ to inhibit growth and induce apoptosis in gastric cancer cells [135], antagonizes EGFR-dependent Erk1/2 activation in human androgen-independent prostate cancer cells associated with isozyme-selective PKCα inhibition [136], inhibits PKC-catalyzed phosphorylation of a cofactor-independent, arginine-rich protein substrate [137], and inhibits a PKCδ splice variant in 3T3L1 adipocytes indicating its role in controlling obesity [138]. …”