Hydrogen sulfide-induces DNA damage and changes in apoptotic gene expression in human lung fibroblast cells Rajamanickam Baskar, Ling Li and Philip Keith Moore 1 Cardiovascular Biology Research Group, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 1 Correspondence: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Bldg. MD2, 18 Medical Dr., Singapore 117597. E-mail: phchead@nus.edu.sg Hydrogen sulfide (H 2 S) has been shown previously to exert proapoptotic activity. However, the mechanism(s) by which H 2 S affects cell growth and function have not been addressed adequately. In this study, cultured human lung fibroblasts were treated with the H 2 S donor NaHS (10–75 µM; 12–48 h). NaHS caused a concentration-dependent increase in micronuclei formation (indicating DNA damage) and cell cycle arrest (G 1 phase). NaHS increased expression of ku 70 and ku 80 but did not affect the expression of other DNA repair proteins such as proliferating cell nuclear antigen (PCNA) or replication protein A (rNase protection assay). NaHS treatment also resulted in stabilization of p53 coupled with induction of downstream proteins such as p21, Bax, and cytochrome c , as well as translocation of Bax from the cytosol to the mitochondria and release of cytochrome c from mitonchondria. NaHS did not up-regulate cell levels of the antiapoptotic protein, Bcl-2. We propose that the genotoxic action of H 2 S propels the cell toward apoptotic death triggered initially by stabilization of p53 and subsequently involving a cascade of downstream products. These results are of significance as they uncover a hitherto unknown and very fundamental role for H 2 S in determining cell fate.—Baskar, R., Li, L., Moore, P. K. Hydrogen sulfide-induces DNA damage and changes in apoptotic gene expression in human lung fibroblast cells. Key Words: cell cycle • p53 • mitochondria • cytochrome c translocation
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Hydrogen sulfide-induces DNA damage and changes in apoptotic gene expression in human lung fibroblast cells
Baskar, Rajamanickam; Li, Ling; Moore, Philip Keith
Follow The FASEB Journal
, Volume 21 (1): 247
Fed of American Socs for Experimental Biology – Jan 1, 2007
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