Endogenously generated hydrogen peroxide is required for execution of melphalan-induced apoptosis as well as oxidation and externalization of phosphatidylserine.

Hydrogen peroxide (H(2)O(2)) is generated endogenously during execution of both intrinsic as well as extrinsic apoptotic programs suggesting that it may function as a secondary messenger in apoptotic pathways. In the present study, we investigated the role of endogenously generated H(2)O(2) by using two cell lines-HL-60 cells and its subclone, H(2)O(2) resistant HP100 cells overexpressing catalase (CAT). With the exception of CAT, we found no differences in the expression of other primary antioxidant enzymes (Cu/Zn-superoxide dismutase, Mn-superoxide dismutase, and glutathione peroxidase) or apoptosis-related proteins (Bcl-2 and Bax) in HP100 cells as compared with the parental HL-60 cells.

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.

Apoptosis and phagocytosis of apoptotic cells provide for effective and harmless clearance of unwanted or damaged cells in the body. Preferential oxidation of one particular class of phospholipids, phosphatidylserine (PS), is a typical trait of both oxidant- and nonoxidant-induced apoptosis. PS oxidation is likely to play an important role in phagocytosis either by affecting PS externalization acting as an "eat me" signal or by more effective recognition of apoptotic cells by macrophage receptors.