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Ischemic preconditioning: a potential role for protein S-thiolation?
Philip Eaton1, Robert M Bell, Alison C Cave
1Department of Cardiology, King's College London, London, UK. philip.eaton@kcl.ac.uk
Antioxidants & Redox Signaling
|July 7, 2005
Summary
Ischemic preconditioning (IPC) triggers cardioprotection via oxidant stress. This study used biotin-tagged cysteine to identify redox-modified proteins, revealing increased S-thiolation during IPC, which was blocked by antioxidants.
Area of Science:
- Cardiovascular Physiology
- Biochemistry
- Oxidative Stress Research
Background:
- Oxidant stress is integral to ischemic preconditioning (IPC)-induced cardioprotection.
- Identifying specific redox-modified proteins is key to understanding IPC mechanisms.
Purpose of the Study:
- To investigate the role of protein S-thiolation in the triggering of cardioprotection by IPC.
- To identify specific proteins modified by oxidation during IPC.
Main Methods:
- Isolated rat hearts were perfused with biotin-tagged cysteine to label S-thiolated proteins.
- Non-reducing western blots with streptavidin-horseradish peroxidase were used for detection and quantification.
- The effects of preconditioning agonists, antioxidants, and specific inhibitors were assessed.
Main Results:
- IPC significantly increased protein S-thiolation by 160%, an effect blocked by mercaptopropionylglycine.
- Preconditioning agonists and oxidants induced efficient S-thiolation.
- S-thiolation induced by agonists was inhibited by diphenyleneiodonium and bisindolylmaleimide I.
- Nox2 knockout mice showed similar S-thiolation levels to wild-type, suggesting Nox2 is not the sole source of oxidant stress in IPC.
Conclusions:
- Protein S-thiolation is a marker of oxidant stress during IPC and is involved in its triggering.
- The findings implicate specific signaling pathways, including flavoprotein and protein kinase C, in agonist-induced S-thiolation.
- While Nox2-containing NAD(P)H oxidase is a source of oxidant stress, other sources may contribute to IPC-related S-thiolation.