期刊
TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 266, 期 2, 页码 267-275出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2012.10.013
关键词
Particulate matter; Heat shock protein; Air pollution; Arrhythmia; Ca2+/calmodulin-dependent protein kinase II
资金
- Yonsei University College of Medicine [8-2011-0250, 7-2011-0758, 7-2011-0702, 7-2011-0015]
- Basic Science and National Research Program through the National Research Foundation of Korea
- Ministry of Education, Science and Technology [20120007604, 2012045367]
- the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea [A120478]
Ca2+/calmodulin-dependent protein kinase II (CaMKII) is activated by particulate matter (PM) isolated from ambient air and linked to prolonged repolarization and cardiac arrhythmia. We evaluated whether alpha B-crystallin (CryAB), a heat shock protein, could prevent the arrhythmogenic effects of PM by preventing CaMKII activation. CryAB was delivered into cardiac cells using a TAT-protein transduction domain (TAT-CryAB). ECGs were measured before and after tracheal exposure of diesel exhaust particles (DEP) and each intervention in adult Sprague-Dawley rats. After endotracheal exposure of DEP (200 mu g/mL for 30 minutes, n = 11), QT intervals were prolonged from 115 +/- 14 ms to 144 +/- 20 ms (p = 0.03), and premature ventricular contractions were observed more frequently (0% vs. 44%) than control (n = 5) and TAT-Cry (n = 5). However, DEP-induced arrhythmia was not observed in TAT-CryAB (1 mg/kg) pretreated rats (n = 5). In optical mapping of Langendorff-perfused rat heats, compared with baseline, DEP infusion of 12.5 mu g/mL (n = 12) increased apicobasal action potential duration (APD) differences from 2 +/- 6 ms to 36 +/- 15 ms (p < 0.001), APD restitution slope from 0.26 +/- 0.07 to 1.19 +/- 0.11 (p < 0.001) and ventricular tachycardia (VT) from 0% to 75% (p < 0.001). DEP infusion easily induced spatially discordant alternans. However, the effects of DEP were prevented by TAT-CryAB (1 mg/kg, n = 9). In rat myocytes, while DEP increased reactive oxygen species (ROS) generation and phosphated CaMKII, TAT-CryAB prevented these effects. In conclusion, CryAB, a small heat shock protein, might prevent the arrhythmogenic effects of PM by attenuating ROS generation and CaMKII activation. (C) 2012 Elsevier Inc. All rights reserved.
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