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

 Hyelim Park  ;  Sanghoon Park  ;  Hyunju Jeon  ;  Byeong-Wook Song  ;  Jin-Bae Kim  ;  Chang-Soo Kim  ;  Hui-Nam Pak  ;  Ki-Chul Hwang  ;  Moon-Hyoung Lee  ;  Ji Hyung Chung  ;  Boyoung Joung 
 Toxicology and Applied Pharmacology, Vol.266(2) : 267-275, 2013 
Journal Title
 Toxicology and Applied Pharmacology 
Issue Date
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.
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1. College of Medicine (의과대학) > Dept. of Preventive Medicine and Public Health (예방의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
5. Research Institutes (연구소) > Cardiovascular Product Evaluation Center (심혈관제품유효성평가센터) > 1. Journal Papers
Yonsei Authors
Kim, Chang Soo(김창수) ORCID logo https://orcid.org/0000-0002-5940-5649
Park, Hye Lim(박혜림)
Pak, Hui Nam(박희남) ORCID logo https://orcid.org/0000-0002-3256-3620
Song, Byeong Wook(송병욱)
Lee, Moon Hyoung(이문형) ORCID logo https://orcid.org/0000-0002-7268-0741
Jeon, Hyun Ju(전현주)
Joung, Bo Young(정보영) ORCID logo https://orcid.org/0000-0001-9036-7225
Chung, Ji Hyung(정지형)
Hwang, Ki Chul(황기철)
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