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Estrogens Protect Calsequestrin-1 Knockout Mice from Lethal Hyperthermic Episodes by Reducing Oxidative Stress in Muscle

Oxidative stress has been proposed to play a key role in malignant hyperthermia (MH), a syndrome caused by excessive Ca(2+) release in skeletal muscle. Incidence of mortality in male calsequestrin-1 knockout (CASQ1-null) mice during exposure to halothane and heat (a syndrome closely resembling human...

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Autores principales: Michelucci, Antonio, Boncompagni, Simona, Canato, Marta, Reggiani, Carlo, Protasi, Feliciano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610815/
https://www.ncbi.nlm.nih.gov/pubmed/29062464
http://dx.doi.org/10.1155/2017/6936897
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author Michelucci, Antonio
Boncompagni, Simona
Canato, Marta
Reggiani, Carlo
Protasi, Feliciano
author_facet Michelucci, Antonio
Boncompagni, Simona
Canato, Marta
Reggiani, Carlo
Protasi, Feliciano
author_sort Michelucci, Antonio
collection PubMed
description Oxidative stress has been proposed to play a key role in malignant hyperthermia (MH), a syndrome caused by excessive Ca(2+) release in skeletal muscle. Incidence of mortality in male calsequestrin-1 knockout (CASQ1-null) mice during exposure to halothane and heat (a syndrome closely resembling human MH) is far greater than that in females. To investigate the possible role of sex hormones in this still unexplained gender difference, we treated male and female CASQ1-null mice for 1 month, respectively, with Premarin (conjugated estrogens) and leuprolide (GnRH analog) and discovered that during exposure to halothane and heat Premarin reduced the mortality rate in males (79–27% and 86–20%), while leuprolide increased the incidence of mortality in females (18–73% and 24–82%). We then evaluated the (a) responsiveness of isolated muscles to temperature and caffeine, (b) sarcoplasmic reticulum (SR) Ca(2+) release in single fibers, and (c) oxidative stress and the expression levels of main enzymes involved in the regulation of the redox balance in muscle. Premarin treatment reduced the temperature and caffeine sensitivity of EDL muscles, normalized SR Ca(2+) release, and reduced oxidative stress in males, suggesting that female sex hormones may protect mice from lethal hyperthermic episodes by reducing both the SR Ca(2+) leak and oxidative stress.
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spelling pubmed-56108152017-10-23 Estrogens Protect Calsequestrin-1 Knockout Mice from Lethal Hyperthermic Episodes by Reducing Oxidative Stress in Muscle Michelucci, Antonio Boncompagni, Simona Canato, Marta Reggiani, Carlo Protasi, Feliciano Oxid Med Cell Longev Research Article Oxidative stress has been proposed to play a key role in malignant hyperthermia (MH), a syndrome caused by excessive Ca(2+) release in skeletal muscle. Incidence of mortality in male calsequestrin-1 knockout (CASQ1-null) mice during exposure to halothane and heat (a syndrome closely resembling human MH) is far greater than that in females. To investigate the possible role of sex hormones in this still unexplained gender difference, we treated male and female CASQ1-null mice for 1 month, respectively, with Premarin (conjugated estrogens) and leuprolide (GnRH analog) and discovered that during exposure to halothane and heat Premarin reduced the mortality rate in males (79–27% and 86–20%), while leuprolide increased the incidence of mortality in females (18–73% and 24–82%). We then evaluated the (a) responsiveness of isolated muscles to temperature and caffeine, (b) sarcoplasmic reticulum (SR) Ca(2+) release in single fibers, and (c) oxidative stress and the expression levels of main enzymes involved in the regulation of the redox balance in muscle. Premarin treatment reduced the temperature and caffeine sensitivity of EDL muscles, normalized SR Ca(2+) release, and reduced oxidative stress in males, suggesting that female sex hormones may protect mice from lethal hyperthermic episodes by reducing both the SR Ca(2+) leak and oxidative stress. Hindawi 2017 2017-09-10 /pmc/articles/PMC5610815/ /pubmed/29062464 http://dx.doi.org/10.1155/2017/6936897 Text en Copyright © 2017 Antonio Michelucci et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Michelucci, Antonio
Boncompagni, Simona
Canato, Marta
Reggiani, Carlo
Protasi, Feliciano
Estrogens Protect Calsequestrin-1 Knockout Mice from Lethal Hyperthermic Episodes by Reducing Oxidative Stress in Muscle
title Estrogens Protect Calsequestrin-1 Knockout Mice from Lethal Hyperthermic Episodes by Reducing Oxidative Stress in Muscle
title_full Estrogens Protect Calsequestrin-1 Knockout Mice from Lethal Hyperthermic Episodes by Reducing Oxidative Stress in Muscle
title_fullStr Estrogens Protect Calsequestrin-1 Knockout Mice from Lethal Hyperthermic Episodes by Reducing Oxidative Stress in Muscle
title_full_unstemmed Estrogens Protect Calsequestrin-1 Knockout Mice from Lethal Hyperthermic Episodes by Reducing Oxidative Stress in Muscle
title_short Estrogens Protect Calsequestrin-1 Knockout Mice from Lethal Hyperthermic Episodes by Reducing Oxidative Stress in Muscle
title_sort estrogens protect calsequestrin-1 knockout mice from lethal hyperthermic episodes by reducing oxidative stress in muscle
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5610815/
https://www.ncbi.nlm.nih.gov/pubmed/29062464
http://dx.doi.org/10.1155/2017/6936897
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