Role of neuronal calcium sensor-1 as a cardioprotective factor and its possible mechanism.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590293
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: NISHITANI Tomoe 独立行政法人国立循環器病研究センター, 研究所, 室長 (50393244)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: Ca2+シグナル / 心筋 / サバイバル / ミトコンドリア / 酸化ストレス / 虚血―再灌流

Outline of Final Research Achievements

Identifying molecular targets that regulate cardiomyocyte survival is of therapeutic importance for conquering heart failure. Neuronal Ca2+-sensor-1 (NCS-1) is an EF-hand Ca2+-binding protein, which is important for excitable cell functions. Our preliminary results suggest that NCS-1 is involved in stress tolerance in the heart, therefore we examined this hypothesis. We found that NCS-1 deficient (KO) mouse hearts were more susceptible to oxidative (H2O2) and metabolic stress, as well as ischemia-reperfusion injury. Cellular ATP levels, mitochondrial respiration rates (basal and maximal O2 consumption, and proton leak), and activation of Akt survival pathways were significantly depressed in KO myocytes; especially with oxidative stress. These results suggest that NCS-1 plays an important role in mitochondrial detoxification system and hence regulates cardiac survival under stress.

Free Research Field

心臓の細胞生理