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 journalArticle

7 Citations (Scopus)

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 (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
Volume266
Issue number2
DOIs
Publication statusPublished - 2013 Jan 5

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

Fingerprint Dive into the research topics of 'Alpha B-crystallin prevents the arrhythmogenic effects of particulate matter isolated from ambient air by attenuating oxidative stress'. Together they form a unique fingerprint.

  • Cite this