Ischaemic preconditioning preferentially increases protein S-nitrosylation in subsarcolemmal mitochondria. (18th February 2015)

• Record Type: Journal Article
• Authors: Sun, Junhui; Nguyen, Tiffany; Aponte, Angel M.; Menazza, Sara; Kohr, Mark J.; Roth, David M.; Patel, Hemal H.; Murphy, Elizabeth; Steenbergen, Charles
• Is Part Of: Cardiovascular research. Volume 106:Number 2(2015)
• Page Start: 227
• Page End: 236
• Publication Date: 2015-02-18
• Subjects: Protein S-nitrosylation -- Ischaemic preconditioning -- Caveolae -- Subsarcolemmal and interfibrillar mitochondria; Cardiovascular system -- Diseases -- Periodicals; Cardiovascular system -- Periodicals; 616.1
• DOI: 10.1093/cvr/cvv044
• Languages: English
• ISSNs: 0008-6363

Abstract

Abstract: Nitric oxide (NO) and protein S -nitrosylation (SNO) have been shown to play important roles in ischaemic preconditioning (IPC)-induced acute cardioprotection. The majority of proteins that show increased SNO following IPC are localized to the mitochondria, and our recent studies suggest that caveolae transduce acute NO/SNO cardioprotective signalling in IPC hearts. Due to the close association between subsarcolemmal mitochondria (SSM) and the sarcolemma/caveolae, we tested the hypothesis that SSM, rather than the interfibrillar mitochondria (IFM), are major targets for NO/SNO signalling derived from caveolae-associated eNOS. Following either control perfusion or IPC, SSM and IFM were isolated from Langendorff perfused mouse hearts, and SNO was analysed using a modified biotin switch method with fluorescent maleimide fluors. In perfusion control hearts, the SNO content was higher in SSM compared with IFM (1.33 ± 0.19, ratio of SNO content Perf-SSM vs. Perf-IFM), and following IPC SNO content significantly increased preferentially in SSM, but not in IFM (1.72 ± 0.17 and 1.07 ± 0.04, ratio of SNO content IPC-SSM vs. Perf-IFM, and IPC-IFM vs. Perf-IFM, respectively). Consistent with these findings, eNOS, caveolin-3, and connexin-43 were detected in SSM, but not in IFM, and IPC resulted in a further significant increase in eNOS/caveolin-3 levels in SSM. Interestingly, we did not observe an IPC-induced increase in SNO or eNOS/caveolin-3 in SSM isolated from caveolin-3 −/− mouse hearts, which could not be protected with IPC. In conclusion, these results suggest that SSM may be the preferential target of sarcolemmal signalling-derived post-translational protein modification (caveolae-derived eNOS/NO/SNO), thus providing an important role in IPC-induced cardioprotection.