Regulation of heat shock-induced apoptosis by sensitive to apoptosis gene protein.
Heat shock may increase oxidative stress due to increased production of reactive oxygen species and/or the promotion of cellular oxidation events. Sensitive to apoptosis gene (SAG) protein, a novel zinc RING finger protein that protects mammalian cells from apoptosis by redox reagents, is a metal chelator and a potential reactive oxygen species scavenger, but its antioxidant properties have not been completely defined. In this report, we demonstrate that modulation of SAG expression in U937 cells regulates heat shock-induced apoptosis. When we examined the protective role of SAG against heat shock-induced apoptosis with U937 cells transfected with the cDNA for SAG, a clear inverse relationship was observed between the amount of SAG expressed in target cells and their susceptibility to apoptosis. We also observed a significant decrease in the endogenous production of reactive oxygen species and oxidative DNA damage in SAG-overexpressed cells compared to control cells on exposure to heat shock. In addition, transfection of PC3 cells with SAG small interfering RNA markedly decreased the expression of SAG, enhancing the susceptibility of heat shock-induced apoptosis. Taken together, these results indicate that SAG may play an important role in regulating the apoptosis induced by heat shock presumably through maintaining the cellular redox status.
Lee
Sun Joo
SJ
School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University, Taegu 702-701, Korea.
Yang
Eun Sun
ES
Kim
Sun Yee
SY
Kim
Sung Youl
SY
Shin
Seoung Woo
SW
Park
Jeen-Woo
JW
D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D005434:Flow Cytometry; D018869:Heat-Shock Response / Q000502:physiology*; D006358:Hot Temperature / Q000009:adverse effects*; D006801:Humans; D015151:Immunoblotting; D008928:Mitochondria / Q000473:pathology; D010084:Oxidation-Reduction; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C118307:RNF7 protein, human; D044767:Ubiquitin-Protein Ligases