Resveratrol with antioxidant activity inhibits matrix metalloproteinase via modulation of SIRT1 in human fibrosarcoma cells

Life Sciences ◽  
2011 ◽  
Vol 88 (11-12) ◽  
pp. 465-472 ◽  
Author(s):  
Soo-Jin Lee ◽  
Moon-Moo Kim
Author(s):  
Wesam Bassiouni ◽  
John M. Seubert ◽  
Richard Schulz

Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein which mediates staurosporine (STS)-induced cell death. AIF cleavage and translocation to the cytosol is thought to be calpain-1-dependent as calpain inhibitors reduced AIF proteolysis. However, many calpain inhibitors also inhibit matrix metalloproteinase-2 (MMP-2) activity, an intracellular and extracellular protease implicated in apoptosis. Here we investigated whether MMP-2 activity is affected in response to STS and if contributes to AIF cleavage. Human fibrosarcoma HT1080 cells were treated with STS (0.1 µM, 0.25-24 hr). A significant increase in cellular MMP-2 activity was seen by gelatin zymography after 6 hr STS treatment, prior to induction of cell necrosis. Western blot showed the time-dependent appearance of two forms of AIF (~60 and 45 kDa) in the cytosol which were significantly increased at 6 hr. Surprisingly, knocking down MMP-2 or inhibiting its activity with MMP-2 preferring inhibitors ARP-100 or ONO-4817, or inhibiting calpain activity with ALLM or PD150606, did not prevent the STS-induced increase in cytosolic AIF. These results show that although STS rapidly increases MMP-2 activity, the cytosolic release of AIF may be independent of the proteolytic activities of MMP-2 or calpain.


PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e67766 ◽  
Author(s):  
Michael J. Herr ◽  
Jayaprakash Kotha ◽  
Nikolaus Hagedorn ◽  
Blake Smith ◽  
Lisa K. Jennings

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