17-β estradiol attenuates ovariectomy-induced changes in cardiomyocyte contractile function via activation of AMP-activated protein kinase.

Autor: Turdi S; Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071, USA., Huff AF; Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071, USA., Pang J; Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071, USA; Department of Emergency, Qilu Hospital of Shandong University, Jinan, Shandong 250012, PR China., He EY; Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071, USA., Chen X; Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071, USA; Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China., Wang S; Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071, USA., Chen Y; Department of Emergency, Qilu Hospital of Shandong University, Jinan, Shandong 250012, PR China., Zhang Y; Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071, USA; Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China., Ren J; Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071, USA; Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: jren@uwyo.edu.
Jazyk: angličtina
Zdroj: Toxicology letters [Toxicol Lett] 2015 Jan 05; Vol. 232 (1), pp. 253-62. Date of Electronic Publication: 2014 Nov 13.
DOI: 10.1016/j.toxlet.2014.11.012
Abstrakt: Menopause increases the risk of cardiometabolic diseases in women. This circumstance is usually attributed to a deficiency in circulating estrogen levels although the underlying mechanism remains elusive. Given the pivotal role of AMP-activated protein kinase (AMPK) in the regulation of energy metabolism and cardiac function, this study was designed to examine the role of AMPK in estrogen deficiency and replacement-exerted cardiomyocyte responses. Adult female WT and AMPK kinase dead (KD) mice were subjected to bilateral ovariectomy (OVX) or sham operation. A cohort of ovariectomized mice received 17β-estradiol (E2) (40μg/kg/day, i.p.) for 6 weeks. Mechanical and intracellular Ca(2+) properties were evaluated including peak shortening (PS), time-to-PS (TPS), time-to-90%-relengthening (TR90), and maximal velocity of shortening/relengthening (±dL/dt). Levels of AMPK, Akt JNK, ACC, SERCA, membrane Glut4, AS160 and PGC-1α were assessed using Western blot. OVX significantly decreased PS, ±dL/dt and intracellular Ca(2+) rise in responsible to electric stimulus, prolonged TR90 and intracellular Ca(2+) decay without affecting TPS and resting intracellular Ca(2+), the effects of which were reconciled by E2 replacement. Western blot analysis depicted that OVX suppressed phosphorylation of Akt AMPK and ACC although it promoted JNK phosphorylation, the effects of which were mitigated or significantly attenuated by E2 treatment in WT but not KD mice. Moreover, OVX procedure downregulated SERCA2a and membrane Glut4 while inhibiting AS160 phosphorylation without affecting PGC-1α levels. In vitro study revealed that E2 corrected cardiomyocyte contractile dysfunction elicited by OVX in cardiomyocytes from WT but not the AMPK kinase dead mice. Taken together, these data suggest that E2 treatment ameliorates estrogen deficiency-induced changes in cardiac contractile function possibly through an AMPK-dependent mechanism.
(Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
Databáze: MEDLINE
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