性別の影響 [Ca(2+) ](i) メタボリック阻害中のミオサイトでNa(+) -Ca(2+) 交換器を過剰発現する
K Sugishita1, Z Su, F Li
1Division of Cardiology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA.
Circulation
|October 24, 2001
まとめ
性別とエストロゲンは,代謝ストレス中の心臓カルシウム処理に大きく影響します. エストロゲンは,細胞内ナトリウムとカルシウムの増加を男性筋細胞に減少させ,性差を軽減します.
科学分野:
- 心血管生理学 心血管の生理学
- 細胞電気生理学 細胞電気生理学
- 分子心臓病学 分子心臓病学
背景:
- Na ((+) - Ca ((2+) 交換器 (NCX) は,心臓のカルシウム過負荷と損傷に役割を果たします.
- NCXの過剰発現は,雄性および卵巣切除された雌性マウスでは,イシュケミア/再注射損傷を悪化させるが,無傷の雌性マウスではそうではない.
研究 の 目的:
- メタボリック阻害 (MI) 中の細胞内カルシウム ([Ca(2+) ](i)) とナトリウム ([Na(+) ](i)) レベルに対する性別とエストロゲンの影響を調査する.
- NCXを過剰発現する野生型 (WT) と変異型 (TG) のマウスにおけるこれらの効果を比較する.
主な方法:
- フロオ3とナトリウム緑を用いたフローサイトメトリーで[Ca2+]と[Na+]を測定する.
- メタボリック阻害 (MI) は,雄性および雌性WTおよびTGマウスからのミオサイトに誘発されました.
- KB-R7943.3を使用したNCXの薬理学的抑制.
主要な成果:
- 男性のTGミオサイトは,男性WTミオサイトと比較して,MIの間,著しく高い[Ca2+]を呈した.
- NCX過剰発現は,女性ミオサイトにおけるMI中に[Ca2+]を有意に増加させなかった.
- MI中の[Ca2+]と[Na+]の上昇は,女性のミオサイトよりも男性のミオサイトで大きかった.
- エストロゲンは,MI中の男性筋細胞における[Ca2+]と[Na+]の増加を弱め,[Na+]の性別差をなくした.
結論:
- NCX発現の増加は,メスマウスミオサイトと比較して,男性でのMI中に[Ca2+]のより顕著な上昇につながります.
- エストロゲンは,この性別の違いを媒介し,部分的には,MI中に重要なNCX変容体である[Na(+) ](iの上昇を阻害することによって,MIを媒介します.
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