Premium
Preconditioning increases S‐nitrosylation of L‐type calcium channel and SERCA2a
Author(s) -
Sun Junhui,
Steenbergen Charles,
Murphy Elizabeth
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1379
Subject(s) - s nitrosylation , ischemic preconditioning , chemistry , nitric oxide , nitrosylation , perfusion , ischemia , medicine , calcium , l type calcium channel , calcium channel , biochemistry , cysteine , enzyme
Nitric oxide has been shown to be an important signaling messenger in ischemic preconditioning (IPC). Accordingly, we investigated whether protein S‐nitrosylation occurs in IPC hearts, and if so to identify S‐nitrosylation modified proteins. C57BL/6J mouse hearts were subjected to 20 min of Langendorff perfusion, 4 cycles of IPC (5 min of no‐flow ischemia and 5 min of perfusion), 20 min of no‐flow ischemia, and 40 min of reperfusion. Recovery of post‐ischemic left ventricular developed pressure (LVDP) was expressed as a percentage of pre‐ischemic LVDP. Compared with non‐IPC group, IPC significantly increase the recovery of LVDP after ischemic reperfusion (56.7+/−6.7% (n=10) vs 39.8+/−4.5% (n=8)). IPC significantly increased the S‐nitrosothiol (SNO) content of heart membrane fractions from 3.4+/−0.6 (n=6) pmol/mg protein in perfusion control to 9.9+/−0.4 (n=5) pmol/mg protein in IPC hearts. By biotin switch method, the L‐type calcium channel alpha 1 subunit was identified as the predominant S‐nitrosylated protein, and the level of protein S‐nitrosylation was significantly increased by IPC. Other S‐nitrosylated proteins identified by proteomic analysis in IPC hearts include SERCA2a, glycogen phosphorylase, oxoglutarate dehydrogenase, alpha myosin heavy chain and myomesin‐2. The increase of SNO contents in IPC hearts suggest that protein S‐nitrosylation may play an important role in IPC. The data suggest that protein S‐nitrosylation might elicit its cardioprotective effect by regulating cardiac intracellular calcium handling, energy metabolism, and sarcomeric ultrastructure.