کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2597064 1562402 2008 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inhibition of cation channels and suicidal death of human erythrocytes by zidovudine
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Inhibition of cation channels and suicidal death of human erythrocytes by zidovudine
چکیده انگلیسی

Zidovudine, a drug widely used in the treatment of AIDS, has been shown to influence cytosolic calcium activity in HIV-infected lymphocytes. Thus, zidovudine may modify the activity of Ca2+-permeable ion channels. In erythrocytes, activation of Ca2+-permeable cation channels stimulates eryptosis, the suicidal erythrocyte death. Eryptosis is characterized by cell shrinkage (apparent from a decrease of forward scatter) and phosphatidylserine (PS) exposure (apparent from annexin V-binding) at the erythrocyte surface. Triggers of eryptosis include isotonic cell shrinkage (Cl− replacement by gluconate), energy depletion (removal of glucose) or exposure to a variety of drugs including azathioprine. The present study explored, whether zidovudine influences the activity of erythrocytic Ca2+-permeable cation channels and eryptosis. Whole-cell patch-clamp recordings indeed revealed that zidovudine blocked the Ca2+-permeable cation channels activated by Cl− removal. In the presence of Cl− and glucose, the percentage of annexin V-binding cells was low and not significantly modified by the presence of zidovudine. Both, Cl− removal and glucose depletion increased annexin V-binding and decreased forward scatter, effects significantly blunted by zidovudine (2 μg/ml). According to Fluo3 fluorescence, zidovudine (2 μg/ml) did not significantly modify cytosolic Ca2+ concentration under control conditions, but significantly blunted the increase in cytosolic Ca2+ activity following glucose depletion. Furthermore, zidovudine significantly inhibited azathioprine-induced eryptosis. The present observations disclose a completely novel effect of zidovudine, i.e. its inhibitory influence on Ca2+ entry and subsequent suicidal erythrocyte death during isotonic cell shrinkage or energy depletion.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 253, Issues 1–3, 20 November 2008, Pages 62–69
نویسندگان
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