Versican protects cells from oxidative stress-induced apoptosis.
Oxidant injury plays a critical role in the degenerative changes that are characterized by a decline in parenchymal cell numbers and viability, and occur with aging and in the etiology of many diseases. The extracellular proteoglycan versican is widely distributed in the extracellular matrix surrounding the cells. This study examines whether versican plays a role in protecting cells from free radical-induced apoptosis. Stable expression of versican or its C-terminal domain significantly decreased H(2)O(2)-induced cellular apoptosis. Cells in adherent monolayer were more resistant to H(2)O(2)-induced apoptosis than cells cultured in suspension. While vigorous trypsinization caused integrin cleavage and rendered the cells more susceptible to H(2)O(2)-induced damages, expression of versican or its C-terminal domain enhanced cell attachment and expression of beta1 integrin and fibronectin. Enhanced cell-matrix interaction by addition of manganese (MnCl(2)) to cultures also significantly diminished H(2)O(2)-induced apoptosis. The results suggest that versican plays an important role in reducing oxidant injury through an enhancement of cell-matrix interaction.
Wu
Yaojiong
Y
Sunnybrook and Women's College Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario, Canada M4N 3M5.
Wu
Jin
J
Lee
Daniel Y
DY
Yee
Albert
A
Cao
Liu
L
Zhang
Yaou
Y
Kiani
Chris
C
Yang
Burton B
BB
D017304:Annexin A5 / Q000737:chemistry; D017209:Apoptosis; D001254:Astrocytoma / Q000378:metabolism; D015153:Blotting, Western; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002469:Cell Separation; D002470:Cell Survival; D002712:Chlorides / Q000494:pharmacology; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005353:Fibronectins / Q000737:chemistry / Q000378:metabolism; D005434:Flow Cytometry; D005609:Free Radicals; D006025:Glycosaminoglycans / Q000737:chemistry; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000494:pharmacology; D019012:Integrin beta1 / Q000378:metabolism; D037181:Lectins, C-Type; D008345:Manganese / Q000737:chemistry; D017895:Manganese Compounds / Q000494:pharmacology; D016877:Oxidants / Q000737:chemistry; D018384:Oxidative Stress; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017382:Reactive Oxygen Species; D019076:Transgenes; D014357:Trypsin / Q000494:pharmacology; D053675:Versicans
D017304:Annexin A5; D002712:Chlorides; D011508:Chondroitin Sulfate Proteoglycans; D005353:Fibronectins; D005609:Free Radicals; D006025:Glycosaminoglycans; D019012:Integrin beta1; D037181:Lectins, C-Type; D017895:Manganese Compounds; D016877:Oxidants; D017382:Reactive Oxygen Species; C508322:VCAN protein, human; D053675:Versicans; D008345:Manganese; D006861:Hydrogen Peroxide; D014357:Trypsin; C025340:manganese chloride