Sex differences in mitochondrial Ca2+ handling in mouse fast-twitch skeletal muscle in vivo
Sex differences in mitochondrial Ca2+ handling in mouse fast-twitch skeletal muscle in vivo
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体内小鼠快肌骨骼肌线粒体 Ca2 处理的性别差异
DOI：
10.1152/japplphysiol.00230.2019
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发表时间：
2020
影响因子：
3.3
通讯作者：
Kano Yutaka
中科院分区：
文献类型：
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作者：
Watanabe Daiki;Hatakeyama Koji;Ikegami Ryo;Eshima Hiroaki;Yagishita Kazuyoshi;Poole David C.;Kano Yutaka
我们研究了小鼠快肌骨骼肌线粒体 Ca2+ 处理特性的性别差异。使用雄性和雌性小鼠的胫骨前肌体内测量细胞质 Ca2+ 浓度（[Ca2+]细胞）的变化。肌肉暴露于浓度不断增加的环匹阿尼酸[CPA；肌浆网 (SR) Ca2+-ATP 酶抑制剂]（10 至 30 至 50 μM，间隔 10 分钟）。治疗30分钟后，男性和女性肌肉中[Ca2+]细胞数分别增加了31.6±2.0%和13.5±4.5%，且性别间存在显着差异。然而，用 10 μM 羰基氰化物-4-（三氟甲氧基）苯腙（线粒体 Ca2+ 摄取抑制剂）将肌肉预孵育 5 分钟，消除了 CPA 诱导的 [Ca2+] 细胞增加方面的性别差异。通过纵向纤维切片评估，女性的肌原纤维间线粒体数量和体积均高于男性（线粒体数量：男性为 13.1±1.0，女性为 19.9±2.3；线粒体体积：男性为 0.034±0.004 μm3/μm3 纤维体积，男性为 0.034±0.004 μm3/μm3 纤维体积）女性纤维体积为0.066 ± 0.008 μm3/μm3，均P<0.05）。 SR Ca2+-ATPase、线粒体 Ca2+ 单向转运蛋白、线粒体融合蛋白 (Mfn) 1 或 Mfn2 的含量没有性别差异。这些结果表明：1) 女性肌细胞的线粒体 Ca2+ 摄取能力高于男性肌细胞，2) 女性肌细胞这种优越的 Ca2+ 摄取能力部分是由于较高的肌原纤维间线粒体含量，而不是与线粒体 Ca2+ 摄取相关的线粒体蛋白的表达。新的和值得注意的这项研究提供的证据表明，女性与男性快肌细胞相比，表现出更强的线粒体钙离子摄取能力，部分原因是较高的肌原纤维间线粒体含量。肌原纤维间线粒体体积密度。
We investigated sex differences in mitochondrial Ca2+handling properties in mouse fast-twitch skeletal muscle. Changes in cytoplasmic Ca2+concentration ([Ca2+]cyto) were measured in vivo using tibialis anterior muscles from male and female mice. The muscles were exposed to increasing concentrations of cyclopiazonic acid [CPA; sarcoplasmic reticulum (SR) Ca2+-ATPase inhibitor] (from 10 to 30 to 50 μM at 10 min intervals). Thirty minutes after treatment, [Ca2+]cytowas increased by 31.6 ± 2.0% and 13.5 ± 4.5% of initial [Ca2+]cytoin male and female muscles, respectively, and there was a significant difference between sexes. However, muscle preincubation for 5 min with 10 μM carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (an inhibitor of mitochondria Ca2+uptake) eradicated this difference between sexes with respect to the CPA-induced [Ca2+]cytoincrease. Both intermyofibrillar mitochondrial number and volume, assessed in longitudinal fiber sections, were higher in females compared with males (mitochondria number: 13.1 ± 1.0 in males vs. 19.9 ± 2.3 in females; mitochondrial volume: 0.034 ± 0.004 μm3/μm3fiber volume in males vs. 0.066 ± 0.008 μm3/μm3fiber volume in females, bothP< 0.05). There were no sex differences in the content of SR Ca2+-ATPase, mitochondrial Ca2+uniporter, mitofusin (Mfn) 1, or Mfn2. These results suggest that1)mitochondrial Ca2+uptake ability is greater in female than male myocytes, and2)this superior Ca2+uptake ability of female myocytes is due, partly, to the higher intermyofibrillar mitochondrial content but not to the expression of mitochondrial proteins related to mitochondrial Ca2+uptake.NEW & NOTEWORTHYThis investigation presents evidence that female versus male fast-twitch muscle exhibits a greater mitochondrial calcium ion uptake capability that is partly conferred by the higher intermyofibrillar mitochondrial volume density.