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Bone morphogenetic protein-2 activates NADPH oxidase to increase endoplasmic reticulum stress and human coronary artery smooth muscle cell calcification.

ABSTRACT: Bone morphogenetic protein-2 (BMP-2) increases oxidant stress and endoplasmic reticulum (ER) stress to stimulate differentiation of osteoblasts; however, the role of these signaling pathways in the transition of smooth muscle cells to a calcifying osteoblast-like phenotype remains incompletely characterized. We, therefore, treated human coronary artery smooth muscle cells (HCSMC) with BMP-2 (100ng/mL) and found an increase in NADPH oxidase activity and oxidant stress that occurred via activation of the bone morphogenetic protein receptor 2 and Smad 1 signaling. BMP-2-mediated oxidant stress also increased endoplasmic reticulum (ER) stress demonstrated by increased expression of GRP78, phospho-IRE1?, and the transcription factor XBP1. Analysis of a 1kb segment of the Runx2 promoter revealed an XBP1 binding site; electrophoretic mobility shift and chromatin immunoprecipitation assays demonstrated that XBP1 bound to the Runx2 promoter at this site in BMP-2-treated HCSMC. Inhibition of oxidant stress or ER stress decreased Runx2 expression, intracellular calcium deposition, and mineralization of BMP-2-treated HCSMC. Thus, in HCSMC, BMP-2 increases oxidant stress and ER stress to increase Runx2 expression and promote vascular smooth muscle cell calcification.

SUBMITTER: Liberman M

PROVIDER: S-EPMC3197703 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Bone morphogenetic protein-2 activates NADPH oxidase to increase endoplasmic reticulum stress and human coronary artery smooth muscle cell calcification.

Liberman Marcel M Johnson Rebecca C RC Handy Diane E DE Loscalzo Joseph J Leopold Jane A JA

Biochemical and biophysical research communications 20110830 3

Bone morphogenetic protein-2 (BMP-2) increases oxidant stress and endoplasmic reticulum (ER) stress to stimulate differentiation of osteoblasts; however, the role of these signaling pathways in the transition of smooth muscle cells to a calcifying osteoblast-like phenotype remains incompletely characterized. We, therefore, treated human coronary artery smooth muscle cells (HCSMC) with BMP-2 (100ng/mL) and found an increase in NADPH oxidase activity and oxidant stress that occurred via activation ...[more]

PMID: 21907184

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Dataset Information

Bone morphogenetic protein-2 activates NADPH oxidase to increase endoplasmic reticulum stress and human coronary artery smooth muscle cell calcification.

Publications

Bone morphogenetic protein-2 activates NADPH oxidase to increase endoplasmic reticulum stress and human coronary artery smooth muscle cell calcification.

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