A novel role for Bcl-2 associated-athanogene-1 (Bag-1) in regulation of the endoplasmic reticulum stress response in mammalian chondrocytes

Ling Yang, Denise McBurney, Shou-Ching Tang, Sara G. Carlson, Walter E. Horton

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

BAG-1 (Bcl-2 associated athanogene-1) is a multifunctional protein, linking cell proliferation, cell death, protein folding, and cell stress. In vivo, BAG-1 is expressed ingrowth plate and articular cartilage, and the expression of BAG-1 is decreased with aging. Chondrocytes respond to endoplasmic reticulum (ER) stress with decreased expression of extracellular matrix proteins, and prolonged ER stress leads to chondrocyte apoptosis. Here we demonstrate for the first time that BAG-1 is involved in ER stress-induced apoptosis in chondrocytes. Induction of ER stress through multiple mechanisms all resulted in downregulation of BAG-1 expression. In addition, direct suppression of BAG-1 expression resulted in chondrocyte growth arrest and apoptosis, while stable overexpression of BAG-1 delayed the onset of ER stress-mediated apoptosis. In addition to regulating apoptosis, we also observed decreased expression of collagen type II in BAG-1 deficient chondrocytes. In contrast, overexpression of BAG-1 resulted in increased expression of collagen type II. Moreover, under ER stress conditions, the reduced expression of collagen type II was delayed in chondrocytes overexpressing BAG-1. These results suggest a novel role for BAG-1 in supporting viability and matrix expression of chondrocytes.

Original languageEnglish (US)
Pages (from-to)786-800
Number of pages15
JournalJournal of cellular biochemistry
Volume102
Issue number3
DOIs
StatePublished - Oct 15 2007

Fingerprint

Endoplasmic Reticulum Stress
Chondrocytes
Collagen Type II
Apoptosis
Protein folding
Extracellular Matrix Proteins
Protein Folding
Cell proliferation
Cartilage
Articular Cartilage
Cell death
Cell Death
Down-Regulation
Aging of materials
Cell Proliferation
Growth

Keywords

  • BAG-1
  • Chondrocytes
  • ER stress

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

A novel role for Bcl-2 associated-athanogene-1 (Bag-1) in regulation of the endoplasmic reticulum stress response in mammalian chondrocytes. / Yang, Ling; McBurney, Denise; Tang, Shou-Ching; Carlson, Sara G.; Horton, Walter E.

In: Journal of cellular biochemistry, Vol. 102, No. 3, 15.10.2007, p. 786-800.

Research output: Contribution to journalArticle

Yang, Ling ; McBurney, Denise ; Tang, Shou-Ching ; Carlson, Sara G. ; Horton, Walter E. / A novel role for Bcl-2 associated-athanogene-1 (Bag-1) in regulation of the endoplasmic reticulum stress response in mammalian chondrocytes. In: Journal of cellular biochemistry. 2007 ; Vol. 102, No. 3. pp. 786-800.
@article{ea49d56197d84ae9bbdfaffd039a739a,
title = "A novel role for Bcl-2 associated-athanogene-1 (Bag-1) in regulation of the endoplasmic reticulum stress response in mammalian chondrocytes",
abstract = "BAG-1 (Bcl-2 associated athanogene-1) is a multifunctional protein, linking cell proliferation, cell death, protein folding, and cell stress. In vivo, BAG-1 is expressed ingrowth plate and articular cartilage, and the expression of BAG-1 is decreased with aging. Chondrocytes respond to endoplasmic reticulum (ER) stress with decreased expression of extracellular matrix proteins, and prolonged ER stress leads to chondrocyte apoptosis. Here we demonstrate for the first time that BAG-1 is involved in ER stress-induced apoptosis in chondrocytes. Induction of ER stress through multiple mechanisms all resulted in downregulation of BAG-1 expression. In addition, direct suppression of BAG-1 expression resulted in chondrocyte growth arrest and apoptosis, while stable overexpression of BAG-1 delayed the onset of ER stress-mediated apoptosis. In addition to regulating apoptosis, we also observed decreased expression of collagen type II in BAG-1 deficient chondrocytes. In contrast, overexpression of BAG-1 resulted in increased expression of collagen type II. Moreover, under ER stress conditions, the reduced expression of collagen type II was delayed in chondrocytes overexpressing BAG-1. These results suggest a novel role for BAG-1 in supporting viability and matrix expression of chondrocytes.",
keywords = "BAG-1, Chondrocytes, ER stress",
author = "Ling Yang and Denise McBurney and Shou-Ching Tang and Carlson, {Sara G.} and Horton, {Walter E.}",
year = "2007",
month = "10",
day = "15",
doi = "10.1002/jcb.21328",
language = "English (US)",
volume = "102",
pages = "786--800",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - A novel role for Bcl-2 associated-athanogene-1 (Bag-1) in regulation of the endoplasmic reticulum stress response in mammalian chondrocytes

AU - Yang, Ling

AU - McBurney, Denise

AU - Tang, Shou-Ching

AU - Carlson, Sara G.

AU - Horton, Walter E.

PY - 2007/10/15

Y1 - 2007/10/15

N2 - BAG-1 (Bcl-2 associated athanogene-1) is a multifunctional protein, linking cell proliferation, cell death, protein folding, and cell stress. In vivo, BAG-1 is expressed ingrowth plate and articular cartilage, and the expression of BAG-1 is decreased with aging. Chondrocytes respond to endoplasmic reticulum (ER) stress with decreased expression of extracellular matrix proteins, and prolonged ER stress leads to chondrocyte apoptosis. Here we demonstrate for the first time that BAG-1 is involved in ER stress-induced apoptosis in chondrocytes. Induction of ER stress through multiple mechanisms all resulted in downregulation of BAG-1 expression. In addition, direct suppression of BAG-1 expression resulted in chondrocyte growth arrest and apoptosis, while stable overexpression of BAG-1 delayed the onset of ER stress-mediated apoptosis. In addition to regulating apoptosis, we also observed decreased expression of collagen type II in BAG-1 deficient chondrocytes. In contrast, overexpression of BAG-1 resulted in increased expression of collagen type II. Moreover, under ER stress conditions, the reduced expression of collagen type II was delayed in chondrocytes overexpressing BAG-1. These results suggest a novel role for BAG-1 in supporting viability and matrix expression of chondrocytes.

AB - BAG-1 (Bcl-2 associated athanogene-1) is a multifunctional protein, linking cell proliferation, cell death, protein folding, and cell stress. In vivo, BAG-1 is expressed ingrowth plate and articular cartilage, and the expression of BAG-1 is decreased with aging. Chondrocytes respond to endoplasmic reticulum (ER) stress with decreased expression of extracellular matrix proteins, and prolonged ER stress leads to chondrocyte apoptosis. Here we demonstrate for the first time that BAG-1 is involved in ER stress-induced apoptosis in chondrocytes. Induction of ER stress through multiple mechanisms all resulted in downregulation of BAG-1 expression. In addition, direct suppression of BAG-1 expression resulted in chondrocyte growth arrest and apoptosis, while stable overexpression of BAG-1 delayed the onset of ER stress-mediated apoptosis. In addition to regulating apoptosis, we also observed decreased expression of collagen type II in BAG-1 deficient chondrocytes. In contrast, overexpression of BAG-1 resulted in increased expression of collagen type II. Moreover, under ER stress conditions, the reduced expression of collagen type II was delayed in chondrocytes overexpressing BAG-1. These results suggest a novel role for BAG-1 in supporting viability and matrix expression of chondrocytes.

KW - BAG-1

KW - Chondrocytes

KW - ER stress

UR - http://www.scopus.com/inward/record.url?scp=35048830516&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35048830516&partnerID=8YFLogxK

U2 - 10.1002/jcb.21328

DO - 10.1002/jcb.21328

M3 - Article

C2 - 17546604

AN - SCOPUS:35048830516

VL - 102

SP - 786

EP - 800

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 3

ER -