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Calreticulin mediates the protective effects of ischemic preconditioning through up‐regulation of thioredoxin in human type II alveolar epithelial cells
Author(s) -
Wang Xian,
Jia Lingyun,
Wang Wang,
Zhen Wei,
Xu Mingjiang,
Zhu Yi
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a449
Subject(s) - thioredoxin , calreticulin , microbiology and biotechnology , ischemia , gene knockdown , a549 cell , chemistry , endogeny , transcription factor , cancer research , oxidative stress , cell , medicine , biology , apoptosis , endoplasmic reticulum , biochemistry , gene
The intracellular mechanisms of ischemic preconditioning (IP) in preventing lung dysfunction following transplantation, shock, and trauma are not well clarified. We found that, compared with prolonged ischemia, IP prior to ischemia up‐regulated calreticulin (CRT) and thioredoxin (TRX) expression in A549 human alveolar type □ epithelial cells. Overexpression of CRT in A549 cells ameliorated ischemia‐induced cell death and promoted TRX transcription via NF‐E2‐related factor 2 (Nrf2). Knockdown of endogenous CRT by siRNA diminished the protective effect of PC and decreased the TRX level. Moreover, overexpression of CRT prevented reactive oxygen species (ROS) formation during ischemia that was reversed by co‐transfecting with a dominant‐negative TRX plasmid. Our results validate CRT as a crucial mediator of the protective effect of IP in alveolar type □ epithelial cells. CRT up‐regulates TRX transcription and subsequently reduces ROS production induced by prolonged ischemia.