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Alternative splicing of key survival genes during adipogenesis
Author(s) -
Patel Niketa A,
Apostolatos Andre,
Li Pengfei,
Watson James,
Cooper Denise
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.922.10
Subject(s) - adipogenesis , gene knockdown , adipocyte , microbiology and biotechnology , biology , alternative splicing , apoptosis , ampk , signal transduction , protein kinase a , kinase , gene , endocrinology , adipose tissue , biochemistry , mesenchymal stem cell , gene isoform
Increased proliferation and differentiation of pre‐adipocytes to mature adipocytes (adipogenesis) within the fat tissues are central to obesity. 3T3‐L1 cell differentiation provides a model parallel to mouse adipogenesis. Pre‐adipocytes undergo apoptosis while mature adipocytes are resistant to apoptosis. The basis for this is poorly understood. Here we demonstrate that terminal adipocyte differentiation is accompanied by alternative expression of apoptosis genes. Our data demonstrate that during adipocyte differentiation between days 4–6, expression of Bcl2 and Bcl‐x, caspase 9 and PKCδ alternatively spliced variants change to its pro‐survival variants along with increases in pBAD, pPTEN and pAKT. Using overexpression and knockdown experiments, we elucidate the link between these genes, adipogenesis and apoptosis. PKCδII, a serine/threonine protein kinase promotes cell survival. Our data points to PKCδII as the signaling kinase upstream of Bcl2‐mediated survival pathway. Natural compounds such as resveratrol and curcumin exhibit anti‐adipogenic activities and promote apoptosis in adipocytes. Our data shows that they inhibit PKCδII expression. Hence, we have identified the intracellular target which is central to pro‐survival pathways in adipocytes that may be modulated to induce anti‐adipogenic effects via splicing. Supported by VA Merit Review Grant (NAP)