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Raloxifene regulates expression of rat heart calcium handling proteins
Author(s) -
Chu Sang Hui,
Goldspink P,
Copits B,
Beck J,
Schwertz D
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.20.4.a257-c
Subject(s) - phospholamban , serca , medicine , endocrinology , chemistry , ovariectomized rat , western blot , calcium , estrogen , phenylephrine , estrogen receptor , calcium channel , atpase , biology , enzyme , biochemistry , gene , blood pressure , cancer , breast cancer
We previously showed that estrogen modulates myocardial calcium‐handling protein (CHP) expression. Here, we examine the comparative effect of the selective estrogen receptor modulator raloxifene (RAL) on CHP abundance. Two weeks after ovariectomy, female rats were treated with either RAL (5mg/kg/d), estradiol benzoate (EB; 16μg/kg/d) or RAL+EB in sesame oil or sesame oil alone (OVX) for another 2 weeks before hearts were harvested to measure β1‐adrenergic receptor (BAR), L‐type Ca2+ channel α1c subunit (Cav1.2), sarcoplasmic reticular Ca2+ATPase (SERCA), and phospholamban (PLB) abundance. A fifth group of rats underwent SHAM surgery (all groups n=6). OVX increased body weight, EB, RAL, and RAL+EB reduced weight compared to OVX though EB was most effective. OVX decreased uterine weight, EB restored weight but RAL and RAL+EB did not. Protein abundance was measured by Western blot and mRNA was quantified by real time RT‐PCR. BAR abundance increased in OVX. EB reversed the increase, RAL did not, and RAL attenuated the EB‐elicited suppression of BAR. OVX, RAL, and RAL+EB increased Cav1.2 abundance, whereas EB returned Cav1.2 abundance to SHAM level. OVX and RAL decreased SERCA abundance whereas ventricular abundance of SERCA in EB and RAL+EB‐treated rats was similar to SHAM. PLB abundance was not altered by any of the treatments. Treatment effects on mRNA levels did not correlate with protein expression. Conclusion: Effect of RAL on myocardial CHP expression is similar to OVX, does not mimic EB, and attenuates the action of EB. Supported by: Falk Medical Research Trust. Raloxifene provided by Eli Lilly Co.