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

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


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 (200μg/mL for 30minutes, n=11), QT intervals were prolonged from 115±14ms to 144±20ms (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 (1mg/kg) pretreated rats (n=5). In optical mapping of Langendorff-perfused rat heats, compared with baseline, DEP infusion of 12.5μg/mL (n=12) increased apicobasal action potential duration (APD) differences from 2±6ms to 36±15ms (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 (1mg/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.

Original languageEnglish
Pages (from-to)267-275
Number of pages9
JournalToxicology and Applied Pharmacology
Issue number2
Publication statusPublished - 2013 Jan 5

Bibliographical note

Funding Information:
This study was supported in part by research grants from Yonsei University College of Medicine ( 8-2011-0250 , 7-2011-0758 , 7-2011-0702 , 7-2011-0015 ), the Basic Science and National Research Program through the National Research Foundation of Korea, funded by the Ministry of Education, Science and Technology ( 20120007604 , 2012045367 ), and a grant from the Korea Health 21 R&D Project , Ministry of Health and Welfare, Republic of Korea ( A120478 ).

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology


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