کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2553816 1124927 2006 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inactivation of H+-vacuolar ATPase by the energy blocker 3-bromopyruvate, a new antitumour agent
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Inactivation of H+-vacuolar ATPase by the energy blocker 3-bromopyruvate, a new antitumour agent
چکیده انگلیسی
3-bromopyruvate (3-Br PA), a strong alkylating agent, was found to cause a dramatic disruption of pH gradients in acidic compartments of Ehrlich ascites tumour cells (EATCs), as well as of rat thymocytes, at concentrations similar to those reported to cause ATP depletion in hepatocellular carcinoma cells. However, in the condition of complete disruption of pH gradients, ATP depletion was not, in either cell type, as serious as pH gradient dissipation. Moreover, the 3-Br PA effect on acidic compartments preceded severe cell ATP depletion, indicating that the former was not merely linked to energy deprivation elicited by 3-Br PA. Experiments conducted on isolated lysosomes supported this view in that the drug inactivated H+-vacuolar ATPase, the enzyme that makes certain compartments in the cell acidic. Inactivation probably involved alkylation of the enzyme on a thiol group, essential for H+-ATPase activity for dithiothreitol secured complete protection from 3-Br PA inactivation. The findings are discussed with regards to a possible involvement of lysosome destabilization in 3-Br PA induced cell death.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Life Sciences - Volume 79, Issue 21, 19 October 2006, Pages 2049-2055
نویسندگان
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