期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 101, 期 15, 页码 5518-5523出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0401175101
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资金
- NHLBI NIH HHS [R01 HL013531, HL13531] Funding Source: Medline
- NIDDK NIH HHS [F32 DK060305, DK60305-02] Funding Source: Medline
- NIGMS NIH HHS [GM 54111, R01 GM054111] Funding Source: Medline
Oxidative stress leads to the up-regulation of many antioxidant enzymes including Cu,Zn superoxide dismutase (SOD1) via transcriptional mechanisms; however, few examples of posttranslational regulation are known. The copper chaperone for SOD1 (CCS) is involved in physiological SOD1 activation, and its primary function is thought to be delivery of copper to the enzyme. Data presented here are consistent with a previously uncharacterized function for CCS in the SOD1 pathway, namely mediating enzyme activation in response to increases in oxygen tension. Activity assays with pure proteins and cell extracts reveal that 02 (or superoxide) is required for activation of SOD1 by CCS. Dose-response studies with a translational blocking agent demonstrate that the cellular oxidative response to O-2 is multitiered: existing apo-pools of SOD1 are activated by CCS in the early response, followed by increasing expression of SOD1 protein with persistent oxidative stress. This CCS function provides oxidant-responsive posttranslational regulation of SOD1 activity and may be relevant to a wide array of physiological stresses that involve a sudden elevation of oxygen availability.
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