Effects of S-Glutathionylation and S-Nitrosylation on Calmodulin Binding to Triads and FKBP12 Binding to Type 1 Calcium Release Channels
P Aracena, W Tang, SL Hamilton… - Antioxidants & redox …, 2005 - liebertpub.com
P Aracena, W Tang, SL Hamilton, C Hidalgo
Antioxidants & redox signaling, 2005•liebertpub.comThis study shows that the combination of glutathione (GSH) plus hydrogen peroxide (H2O2)
promotes the Sglutathionylation of ryanodine receptor type 1 (RyR1) Ca2+ release
channels, and confirms their joint S-glutathionylation and S-nitrosylation by S-
nitrosoglutathione (GSNO). In addition, we show that 35 S-labeled 12-kDa FK506-binding
protein ([35S] FKBP12) bound with a K d of 13.1 n M to RyR1 present in triads or heavy
sarcoplasmic reticulum vesicles; RyR1 S-nitrosylation by NOR-3 or GSNO, but not S …
promotes the Sglutathionylation of ryanodine receptor type 1 (RyR1) Ca2+ release
channels, and confirms their joint S-glutathionylation and S-nitrosylation by S-
nitrosoglutathione (GSNO). In addition, we show that 35 S-labeled 12-kDa FK506-binding
protein ([35S] FKBP12) bound with a K d of 13.1 n M to RyR1 present in triads or heavy
sarcoplasmic reticulum vesicles; RyR1 S-nitrosylation by NOR-3 or GSNO, but not S …
This study shows that the combination of glutathione (GSH) plus hydrogen peroxide (H2O2) promotes the Sglutathionylation of ryanodine receptor type 1 (RyR1) Ca2+ release channels, and confirms their joint S-glutathionylation and S-nitrosylation by S-nitrosoglutathione (GSNO). In addition, we show that 35 S-labeled 12- kDa FK506-binding protein ([35S]FKBP12) bound with a K d of 13.1 nM to RyR1 present in triads or heavy sarcoplasmic reticulum vesicles; RyR1 S-nitrosylation by NOR-3 or GSNO, but not S-glutathionylation, specifically increased by four- to fivefold this K d value. RyR1 redox modifications also increased the K d of [35S]calmodulin binding to triads without affecting B max. RyR1 S-glutathionylation (induced by GSH plus H2O2) or RyR1 S-nitrosylation (produced by NOR-3) increased by approximately six- or twofold, respectively, the K d of apocalmodulin (apoCaM) or Ca2+-calmodulin (CaCaM) binding to triads. Likewise, the combined Sglutathionylation and S-nitrosylation of RyR1 induced by GSNO increased by fourfold the K d of CaCaM binding to triads and abolished apoCaM binding. As both FKBP12 and CaCaM inhibit RyR1, decreased FKBP12 binding to RyR1 and/or decreased CaCaM binding to either RyR1 or dihydropyridine receptor in triad preparations may cause the reported enhanced activation of Ca2+-induced Ca2+ release kinetics mediated by S-glutathionylation/S-nitrosylation. We discuss possible consequences of these redox modifications on RyR1-mediated Ca2+ release in physiological or pathological conditions. Antioxid. Redox Signal. 7, 870–881.
Mary Ann Liebert