Inhibition of NF-κB-dependent Bcl-xL expression by clusterin promotes albumin-induced tubular cell apoptosis

O. Takase, A. W.M. Minto, T. S. Puri, P. N. Cunningham, A. Jacob, M. Hayashi, R. J. Quigg

研究成果: Article査読

59 被引用数 (Scopus)

抄録

Apoptosis and inflammation, important contributors to the progression of chronic kidney disease, can be influenced by clusterin (a secreted glycoprotein that regulates apoptosis) and nuclear factor-κB (NF-κB, a transcription factor modifying the expression of inflammatory genes). We studied proteinuria-induced renal disease and its influence on clusterin-mediated apoptosis. Exposure of cultured mouse proximal tubule epithelial cells to bovine serum albumin (BSA) resulted in activation of NF-κB and activator protein-1 (AP-1) within hours followed by a decline in their activation, decreased activation of extracellular signal-regulated kinases (ERK1/2), decreased cell-associated antiapoptotic Bcl-xL protein but increased apoptosis. Clusterin progressively increased in the media over a 3 day period. Clusterin siRNA blocked protein production, increased NF-κB activation, and significantly increased cellular Bcl-xL protein, thereby reducing spontaneous and BSA-induced apoptosis. An siRNA to the NF-κB inhibitor IκBα had similar results. BSA-stimulated NF-κB activation reciprocally decreased AP-1 activity by preventing ERK1/2 phosphorylation. These in vitro studies suggest that clusterin inhibits NF-κB-mediated antiapoptotic effects by the apparent stabilization of IκBα switching from promoting inflammation to apoptosis during proteinuria.

本文言語English
ページ(範囲)567-577
ページ数11
ジャーナルKidney international
73
5
DOI
出版ステータスPublished - 2008 3月
外部発表はい

ASJC Scopus subject areas

  • 腎臓病学

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