%0 Journal Article %T Molecular nature of sulfhydryl modification by hydrogen peroxide on type 1 ryanodine receptor %A Han Hong-mei %A Wei Ri-sheng %A Lai Anthony F %A Yin Chang-cheng %J Acta Pharmacologica Sinica %D 2016 %B 2016 %9 %! Molecular nature of sulfhydryl modification by hydrogen peroxide on type 1 ryanodine receptor %K %X 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. %U http://www.chinaphar.com/article/view/4015 %V 27 %N 7 %P 888–894 %@ 1745-7254