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Alpha B-crystallin prevents the arrhythmogenic effects of particulate matter isolated from ambient air by attenuating oxidative stress

Authors
 Hyelim Park ; Sanghoon Park ; Boyoung Joung ; Ji Hyung Chung ; Moon-Hyoung Lee ; Ki-Chul Hwang ; Hui-Nam Pak ; Chang-Soo Kim ; Jin-Bae Kim ; Byeong-Wook Song ; Hyunju Jeon 
Citation
 Toxicology and Applied Pharmacology, Vol.266(2) : 267~275, 2013 
Journal Title
 Toxicology and Applied Pharmacology 
ISSN
 0041-008X 
Issue Date
2013
Abstract
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 μg/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 μg/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.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/86261
DOI
10.1016/j.taap.2012.10.013
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Preventive Medicine
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
1. 연구논문 > 1. College of Medicine > Dept. of Life Science
1. 연구논문 > 1. College of Medicine > Yonsei Biomedical Research Center
1. 연구논문 > 5. Research Institutes > Cardiovascular Product Evaluation Center
Yonsei Authors
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Link
 http://www.sciencedirect.com/science/article/pii/S0041008X12004553
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