title: Calumenin has a role in the alleviation of ER stress in neonatal rat cardiomyocytes.
abstract: Disturbance of endoplasmic reticulum (ER) homeostasis causes ER stress (ERS), and triggers the unfolded protein response (UPR) that consequently reduces accumulation of unfolded proteins by increasing the quantity of ER chaperones. Calumenin, a Ca(2+)-binding protein with multiple EF hand motifs, which is located in the ER/SR, is highly expressed during the early developmental stage of the heart, similar to other ER-resident chaperones. The aim of this study was to investigate the functional role of calumenin during ERS in the heart. Like other chaperones (e.g., GRP94 and GRP78), calumenin expression was highly upregulated during ERS induced by 10 μg/ml tunicamycin, but attenuated in the presence of 500 μM PBA, the chemical chaperone in neonatal rat ventricular cardiomyocytes (NRVCs). Upon 7.5-fold overexpression of calumenin using a recombinant adenovirus system, the expression levels of ERS markers (GRP78, p-PERK, and p-elF2α) and ER-initiated apoptosis markers (CHOP and p-JNK) were reduced, whereas the survival protein BCL-2 was upregulated during ERS compared to the control. Evaluation of cell viability by TUNEL assay showed that apoptosis was also significantly reduced by calumenin overexpression in ERS-induced cells. Taken together, our results suggest that calumenin plays an essential role in the alleviation of ERS in neonatal rat cardiomyocytes.
authors.affiliation: School of Life Sciences and Systems Biology Research Center, Gwangju Institute of Science and Technology (GIST), 123 Cheomdan-gwagiro (1 Oryong-dong), Buk-gu, Gwangju 500-712, Republic of Korea.
authors.forename: Joo Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Kwon
authors.forename: Do Han
authors.initials: DH
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
chemical_list: D002135:Calcium-Binding Proteins; C532544:Calu protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; C000717248:Hspa5 protein, mouse
keywords: 4-phenylbutyric acid; ATF; Ad-calu; Ad-lacZ; Apoptosis; C/EBP-homologous protein; CHOP; CREC family proteins; Chaperone; ER-associated degradation; ERAD; ERp57; GRP; IRE; MOI; NRVCs; PBA; PERK; SDS–PAGE; Sarcoplasmic reticulum; TM; TUNEL; Tg; UPR; activating transcription factor; adenovirus containing lacZ gene; adenovirus containing mouse calumenin 1 cDNA; eIF2; eukaryotic initiation factor 2; glucose related protein; ifu; infectious unit; inositol-requiring enzyme; multiplicity of infection; neonatal rat ventricular cardiomyocytes; protein kinase RNA-like endoplasmic reticulum kinase; sodium dodecyl sulfate polyacrylamide gel electrophoresis; terminal deoxynucleotidyl transferase dUTP nick end labeling; thapsigargin; the thiol oxidoreductases proteins disulphide isomerase and ER protein; tunicamycin; unfolded protein response