کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1939093 | 1050753 | 2006 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: CO2 impairs peroxynitrite-mediated inhibition of human caspase-3 CO2 impairs peroxynitrite-mediated inhibition of human caspase-3](/preview/png/1939093.png)
Peroxynitrite (ONOO−) is a transient powerful oxidant produced in vivo as the reaction of nitrogen monoxide (NO) with superoxide (O2-). The peroxynitrite reactivity is modulated by carbon dioxide (CO2) which enhances the peroxynitrite-mediated nitration of aromatics and partially impairs the oxidation of thiols. Here, the effect of CO2 on the peroxynitrite-mediated inhibition of human caspase-3, the execution enzyme of the apoptotic cascade, is reported. Peroxynitrite inhibits the catalytic activity of human caspase-3 by oxidizing the Sγ atom of the Cys catalytic residue. In the absence of CO2, 1.0 equivalent of peroxynitrite inactivates 1.0 equivalent of human caspase-3. In the presence of the physiological concentration of CO2 (=1.3 × 10−3 M), 1.0 equivalent of peroxynitrite inactivates only 0.38 equivalents of human caspase-3. Peroxynitrite affects the kcat value of the human caspase-3 catalyzed hydrolysis of N-acetyl-Asp-Glu-Val-Asp-7-amido-4-methylcoumarin, without altering Km. Both in the absence and presence of CO2, the reducing agent dithiothreitol does not prevent human caspase-3 inhibition by peroxynitrite and does not reverse the peroxynitrite-induced inactivation of human caspase-3. These results represent the first evidence for modulation of peroxynitrite-mediated inhibition of cysteine proteinase action by CO2, supporting the role of CO2 in fine tuning of cell processes (e.g., apoptosis).
Journal: Biochemical and Biophysical Research Communications - Volume 349, Issue 1, 13 October 2006, Pages 367–371