title: Calreticulin translocation aggravates endoplasmic reticulum stress-associated apoptosis during cardiomyocyte hypoxia/reoxygenation.
abstract: BACKGROUND
  Calreticulin (CRT) is major Ca 2+ -binding chaperone mainly resident in the endoplasmic reticulum (ER) lumen. Recently, it has been shown that non-ER CRT regulates a wide array of cellular responses. We previously found that CRT was up-regulated during hypoxia/reoxygenation (H/R) and this study was aimed to investigate whether CRT nuclear translocation aggravates ER stress (ERS)-associated apoptosis during H/R injury in neonatal rat cardiomyocytes.
  
  
  METHODS
  Apoptosis rate and lactate dehydrogenase (LDH) leakage in culture medium were measured as indices of cell injury. Immunofluorescence staining showed the morphological changes of ER and intracellular translocation of CRT. Western blotting or reverse transcription polymerase chain reaction was used to detect the expression of target molecules.
  
  
  RESULTS
  Compared with control, H/R increased apoptosis rate and LDH activity. The ER became condensed and bubbled, and CRT translocated to the nucleus. Western blotting showed up-regulation of CRT, Nrf2, activating transcription factor 4 (ATF4), CHOP and caspase-12 expression after H/R. Exogenous CRT overexpression induced by plasmid transfection before H/R increased cell apoptosis, LDH leakage, ER disorder, CRT nuclear translocation and the expression of ERS-associated molecules. However, administration of the ERS inhibitor, taurine, or CRT siRNA alleviated cell injury, ER disorder, and inhibited ERS-associated apoptosis.
  
  
  CONCLUSIONS
  Our results indicated that during H/R stress, CRT translocation increases cell apoptosis and LDH leakage, aggravates ER disorder, up-regulates expression of nuclear transcription factors, Nrf2 and ATF4, and activates ERS-associated apoptosis.
authors: Fei-Fei
authors: FF
authors: Xu
authors: Department of Pathophysiology; State Key Laboratory of Kidney Disease, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
authors: Xiu-Hua
authors: XH
authors: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D037282:Calreticulin / Q000235:genetics / Q000378:metabolism*; D015687:Cell Hypoxia / Q000235:genetics / Q000502:physiology*; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats
chemical_list: D037282:Calreticulin
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