Abstract
Aim:
To elucidate the molecular nature of sulfhydryl modification by hydrogen peroxide on type 1 ryanodine receptor (RyR1).
Methods:
Rabbit skeletal muscle sarcoplasmic reticulum was treated with hydrogen peroxide, then RyR1 complex was isolated. The proteins in the complex were analysed by electrophoresis, Western blot and electron microscopy.
Results:
(1) Hydrogen peroxide induces inter-subunit cross-linking within the tetrameric RyR1 molecule; (2) in parallel to inter-subunit cross-linking, the RyR1 molecule changes morphology; (3) the chemical and morphological changes are reversible: upon reduction by reducing agents, the RyR1 molecule regains its original state.
Conclusion:
These findings suggest that the molecular mechanism of RyR1 channel activity in sarcoplasmic reticulum regulated by hydrogen peroxide is through inter-subunit cross-linking within the tetrameric RyR1 molecule, which in turn induces structural changes of RyR1.
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Project supported by the British Heart Foundation (PG0303915274) and Medical Research Council (to Anthony F Lai), the National Natural Science Foundation of China (No 30370379 & 30330160) and the Trans-Century Talent Awarding Program, Ministry of Education, China (to Chang-cheng Yin).
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Han, Hm., Wei, Rs., Lai, A. et al. Molecular nature of sulfhydryl modification by hydrogen peroxide on type 1 ryanodine receptor. Acta Pharmacol Sin 27, 888–894 (2006). https://doi.org/10.1111/j.1745-7254.2006.00386.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00386.x
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