Bcl-2 inhibits selective oxidation and externalization of phosphatidylserine during paraquat-induced apoptosis - PubMed (original) (raw)

Bcl-2 inhibits selective oxidation and externalization of phosphatidylserine during paraquat-induced apoptosis

J P Fabisiak et al. Am J Physiol. 1997 Feb.

Abstract

Oxidative stress is a potential component of the final common pathway leading to apoptosis following many diverse stimuli. Here, we document that the oxidant paraquat caused apoptosis in mouse 32D cells. We examined early paraquat-induced lipid peroxidation after metabolic incorporation of the oxidant-sensitive fluorescent fatty acid cis-parinaric acid (cis-PA) into phospholipids and high-performance liquid chromatography separation of specific phospholipid classes. Paraquat induced peroxidation of cis-PA primarily in phosphatidylserine (PS) and to a lesser extent in phosphatidylinositol (PI) within 2 h. The selective oxidation of PS occurred before signs of cytotoxicity and preceded the externalization of PS as assessed by annexin V binding. Overexpression of Bcl-2 afforded significant protection against paraquat-induced apoptosis, early PS and PI oxidation, and PS externalization but not the ultimate formation of high-molecular-weight DNA fragments. Therefore, both selective phospholipid peroxidation and DNA damage occurred after paraquat exposure, but only the former was specifically associated with apoptosis. We suggest Bcl-2 may inhibit oxidant-induced apoptosis by preventing the peroxidation of specific membrane phospholipids.

PubMed Disclaimer

Cited by

Early apoptosis in intestinal and diffuse gastric carcinomas.
Zhou HP, Wang X, Zhang NZ. Zhou HP, et al. World J Gastroenterol. 2000 Dec;6(6):898-901. doi: 10.3748/wjg.v6.i6.898. World J Gastroenterol. 2000. PMID: 11819717 Free PMC article. No abstract available.
Loss of phospholipid asymmetry and elevated brain apoptotic protein levels in subjects with amnestic mild cognitive impairment and Alzheimer disease.
Bader Lange ML, Cenini G, Piroddi M, Abdul HM, Sultana R, Galli F, Memo M, Butterfield DA. Bader Lange ML, et al. Neurobiol Dis. 2008 Mar;29(3):456-64. doi: 10.1016/j.nbd.2007.11.004. Epub 2007 Nov 12. Neurobiol Dis. 2008. PMID: 18077176 Free PMC article.
Abrogation of disease development in plants expressing animal antiapoptotic genes.
Dickman MB, Park YK, Oltersdorf T, Li W, Clemente T, French R. Dickman MB, et al. Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6957-62. doi: 10.1073/pnas.091108998. Epub 2001 May 29. Proc Natl Acad Sci U S A. 2001. PMID: 11381106 Free PMC article.
Mechanism of cytotoxicity of paraquat.
Fukushima T, Tanaka K, Lim H, Moriyama M. Fukushima T, et al. Environ Health Prev Med. 2002 Jul;7(3):89-94. doi: 10.1265/ehpm.2002.89. Environ Health Prev Med. 2002. PMID: 21432289 Free PMC article.

Bcl-2 inhibits selective oxidation and externalization of phosphatidylserine during paraquat-induced apoptosis - PubMed (original) (raw)