Oxidized-mediated cell death

Their role in oxidized-mediated cell death is also assessed (i) by the protective effect of antioxidants which reduce or inhibit oxidized LDL-induced ROS generation, caspase activation and subsequent apoptosis. 

More needs to be learned about the role of NO in oxidatively-mediated cell death before it can be used in clinical medicine. The factors that determine under which conditions it is an antioxidant vs prooxidant need to be elucidated since they are likely to include more than just the concentration of NO (Rubbo el al., 1994). For example, the augmenting or mitigating response may also depend upon the nature of the oxidative stress or diseased cell type. 

Work in several laboratories including our own has shown that polyunsaturation correlates with change in susceptibility to oxidant-mediated cytotoxicity and decreased cell survival (Wagner et al, 1993 Buettner, 1993 Wagner eta/., 1992 Spitz etal, 1992 Hart eta/., 1991 Guffyefa/., 1984). The quantitative observation on the relationship of fc/y-allylic positions and oxidizability provides a rational basis for understanding the role of polyunsaturation in oxidation-related cell death. 

Polyphenols and flavonoids present in red wine and grape juice, fruits and vegetables, have potent antioxidant activity, which may slow down oxidative modification of LDL, and their subsequent toxicity (Wedworth and Lynch, 1995). Phenolic compounds exert cytoprotection on vascular cultured cells by inhibiting the calcium rise and subsequent oxidized LDL-mediated cell death (Vieira et al, 1998). These compounds may play a role in the relatively low level of coronary heart disease in Prance ( Fnench Paradox ) and other Mediterranean countries (Renaud and Ruf, 1994). 

Apoptotic cell death is regulated by NO and ONOO" in several cell types including myeloid-derived leukocytes such as neutrophils. The biological effects of NO and ONOO" have been recently reviewed [68]. GEA3162 is able to promote apoptotic cell death in human neutrophils in a caspase-dependent manner [69]. The tumor suppressor p53 is suggested to play a crucial role in apoptosis induced by oxidants. However, functional p53 is not a requirement for ONOO -mediated cell death, as GEA3162 induces mitochondrial permeability in a p53-deficient murine bone marrow cell line, Jaws II. GEA3162 activates caspases 3 and 2 which are important for apoptosis to proceed, with roles for caspases 8 and 9, and p38 MAP kinase [70]. 

Virag L, Salzman AL, Szabo C. Poly (ADP-ribose) synthetase activation mediates mitochondrial injury during oxidant-induced cell death. J Immunol 1998 161(7) 3753-3759. 

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