期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 48, 期 11, 页码 1548-1558出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2010.02.038
关键词
Cytochrome P450; Gene expression; Heat shock protein; Heme; Hemoglobin; Free radicals
资金
- National Institutes of Health [CA53914, GM51491, HL076491]
- NATIONAL CANCER INSTITUTE [R01CA053914, R29CA053914] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL076491] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM051491] Funding Source: NIH RePORTER
Although the insertion of heme into proteins enables their function in bioenergetics, metabolism, and signaling, the mechanisms and regulation of this process are not fully understood. We developed a means to study cellular heme insertion into apo-protein targets over a 3-h period and then investigated how nitric oxide (NO) released from a chemical donor (NOC-18) might influence heme (protoporphyrin IX) insertion into seven targets that present a range of protein structures, heme ligation states, and functions (three NO synthases, two cytochrome P450's, catalase, and hemoglobin). NO blocked cellular heme insertion into all seven apo-protein targets. The inhibition occurred at relatively low (nM/min) fluxes of NO, was reversible, and did not involve changes in intracellular heme levels, activation of guanylate cyclase, or inhibition of mitochondrial ATP production. These aspects and the range of protein targets suggest that NO can act as a global inhibitor of heme insertion, possibly by inhibiting a common step in the process. (C) 2010 Elsevier Inc. All rights reserved.
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