Redox reactions have been shown to modulate sarcoplasmic reticulum (SR) functions, and Ca2+-signals can elicit the generation of reactive oxygen species. Therefore, cellular redox- and Ca2+-signaling processes may functionally interact with each other. To test the hypothesis that altered SR functions may send signals to modulate cellular redox status, we studied transgenic mice overexpressing cardiac calsequestrin (CSQ), a Ca2+-binding protein in the SR. RT-PCR analysis showed that mRNA expression of a redox-sensitive gene, c-fos was highly induced in CSQ-overexpressing hearts compared to junctin-overexpressing or non-transgenic hearts. Surprisingly, protein carbonyl content was found to be lower in CSQ-overexpressing hearts, suggesting that CSQ-overexpressing cells may be in a highly reductive state. Therefore, reductive-signals may be responsible for the induction of c-fos expression. Further, since the inclusion of thiols in internal solutions suppressed Ca2+-induced Ca2+ release (CICR) in whole cell-clamped myocytes, changes in cellular redox status may be responsible for the impairment of CICR that was previously observed in CSQ-overexpressing myocytes. Expression levels of Cu,Zn-SOD, Mn-SOD, catalase and GSH peroxidase were not different in CSQ-overexpressing compared to non-transgenic hearts, suggesting that altered cellular redox status is not due to adaptive changes in antioxidant enzyme levels. These results are the first to demonstrate evidence of a possible cross talk between the SR and cellular redox-signaling.
|Original language||English (US)|
|State||Published - Mar 20 1998|
ASJC Scopus subject areas
- Molecular Biology