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Calcium regulates SERCA2 transcription in cardiomyocytes
Author(s) -
ZarainHerzberg Angel,
Rodríguez Gabriela
Publication year - 2006
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.20.5.a1340-a
Subject(s) - calcium , transcription (linguistics) , chemistry , microbiology and biotechnology , calcium signaling , biophysics , medicine , biology , philosophy , linguistics
The sarcoplasmic reticulum (SR) Ca 2+ ‐ATPase (SERCA2) determines the rate of contraction and relaxation of the cardiomyocyte. Transient elevation of intracellular calcium ([Ca 2+ ] i ) is an important mechanism for cell signaling. In PC12 cells, depletion of endoplasmic reticulum Ca 2+ by EGTA led to an increase in SERCA2 Ca 2+ transport. In vascular smooth muscle cells in culture thapsigargin (Tg), A23187 and extracellular calcium increased the level of SERCA2 mRNA and Ca 2+ chelation prevented such increase, possibly involving a protein kinase mechanism. In cardiomyocytes in culture was reported that depletion of SR Ca 2+ by Tg led to increase SERCA2 expression via an endoplasmic reticulum stress response element in the proximal promoter of SERCA2 that may bind ATF6. However, it is not clear the role of [Ca 2+ ] i in regulating the expression of SERCA2 gene in cardiomyocytes. The goal of this work is to study the role of [Ca 2+ ] i on SERCA2 gene transcription in cardiomyocytes in culture. We analyzed the transcription of SERCA2 using human promoter gene constructs in cardiomyocytes under various culture conditions. Treatment of cardiomyocytes in culture with Tg, A23187, and ryanodine, increased SERCA2 transcription 3‐ and 2‐fold, respectively. In contrast, EGTA and BAPTA reduced SERCA2 transcription activity by 50% and 80%, respectively. Addition of 5 mM CaCl 2 to the culture media increased 1.5 to 2‐fold SERCA2 transcription. In order to clarify if the increase in SERCA2 transcription is due to transient increase in [Ca 2+ ] i , we down‐regulated endogenous SERCA2 expression by endogenous transcription of small interference SERCA2 RNA delivered by adenoviral infection of cardiomyocytes in culture. The transcriptional activity of the SERCA2 gene was increased 2.5‐fold, 72h after infection.