EurekaMag.com logo
+ Site Statistics
References:
52,725,316
Abstracts:
28,411,598
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on Google+Follow on Google+
Follow on LinkedInFollow on LinkedIn

+ Translate

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


American Journal of Physiology 272(2 Pt 1): C675-C684
Bcl-2 inhibits selective oxidation and externalization of phosphatidylserine during paraquat-induced apoptosis
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.


Accession: 002763186

PMID: 9124312



Related references

Selective oxidation and externalization of membrane phosphatidylserine: Bcl-2-induced potentiation of the final common pathway for apoptosis. Brain Research 831(1-2): 125-130, June 12, 1999

Selective oxidation and externalization of membrane phosphatidylserine: Bcl-2-induced potentiation of the final common pathway for apoptosis. Brain Research 831(1-2): 125-130, 1999

Vitamin E inhibits anti-Fas-induced phosphatidylserine oxidation but does not affect its externalization during apoptosis in Jurkat T cells and their phagocytosis by J774A.1 macrophages. Antioxidants & Redox Signaling 6(2): 227-236, 2004

Lipid antioxidant, etoposide, inhibits phosphatidylserine externalization and macrophage clearance of apoptotic cells by preventing phosphatidylserine oxidation. Journal of Biological Chemistry 279(7): 6056-6064, 2003

Endogenously generated hydrogen peroxide is required for execution of melphalan-induced apoptosis as well as oxidation and externalization of phosphatidylserine. Chemical Research in Toxicology 17(5): 685-696, 2004

Lack of phosphatidylserine externalization in etoposide-induced apoptotic cells is related to its antioxidant protection of phosphatidylserine oxidation. Toxicological Sciences 72(S-1): 353, March, 2003

Paraquat-induced phosphatidylserine oxidation and apoptosis are independent of activation of PLA2. American Journal of Physiology 274(5 Pt 1): L793-L802, 1998

Fas-triggered oxidation of phosphatidylserine is essential for its externalization during apoptosis in lung epithelial carcinoma A-549 cells undergoing Fas-mediated apoptosis. Toxicological Sciences 72(S-1): 353, March, 2003

A role for oxidative stress in apoptosis: oxidation and externalization of phosphatidylserine is required for macrophage clearance of cells undergoing Fas-mediated apoptosis. Journal of Immunology 169(1): 487-499, 2002

Etoposide inhibits phosphatidylserine oxidation, externalization, and recognition of apoptotic HL-60 cells by macrophages. Proceedings of the American Association for Cancer Research Annual Meeting 44: 1016, July, 2003