[Role of xanthine oxidase and xanthine dehydrogenase systems in thymocyte apoptosis, induced by papaverine].
It has been established that papaverine as well as other xenobiotics (dexamethasone and nitrosodimethylamine) [figure: see text] provoked the thymocyte death like apoptosis. The increase of the quantity of double-strand, single-strand DNA breaks and low molecular weight fragments of DNA preceded cell death. In papaverine-induced process of thymocyte apoptosis the total activity of xanthine oxidase in thymocytes strongly elevated long before their death, the conversion of xanthine dehydrogenase (D-form) to xanthinoxidase (O-form) and accumulation of O-form in the cultural medium took place. Direct stimulating effect of papaverine on O-form of enzyme in thymocyte lysate was revealed. The used digitonin thymocytes were divided into cytoplasmic and structural component fractions. It was shown that about 80% of total xanthinoxidase activity was concentrated in cytoplasma while only 20% of its activity was found in structural components. More higher ratio of xanthinoxidase/xanthindehydrogenase (XO/XDH) was observed and papaverine-induced changes of these enzyme forms activities were expressed more brightly in the structural components, than in the thymocyte cytoplasma. During the process of developing thymocytes apoptosis caused by papaverine the reaction of lipid peroxidation was intensified. XO-hypoxanthin system displaying prooxidant influence on cells increased the cytotoxic effect of papaverine but the presence of allopurinol or catalase and superoxidedismutase decreased it. Besides, cytotoxic action on thymocytes of allopurinol itself as well as hypoxanthin itself was revealed.
Kishko
T O
TO
L. I. Medved Institute of Ecohygiene and Toxicology, Ukraine, Kyiv.mmarch@chdu.cv.ua
Dmitrenko
N P
NP
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015227:Lipid Peroxidation; D010208:Papaverine / Q000494:pharmacology*; D051381:Rats; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014968:Xanthine Dehydrogenase / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism*
D010208:Papaverine; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase
Rol' ksantinoksidaznoĭ i ksantindegidrogenaznoĭ sistem v apoptoze timotsitov, indutsirovannom papaverinom.