Molecular mechanisms underlying the promotion of wound repair by coenzyme Q10: PI3K/Akt signal activation via alterations to cell membrane domains.
Molecular mechanisms underlying the promotion of wound repair by coenzyme Q10: PI3K/Akt signal activation via alterations to cell membrane domains.
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辅酶 Q10 促进伤口修复的分子机制：通过改变细胞膜结构域激活 PI3K/Akt 信号。
DOI：
10.3164/jcbn.21-141
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发表时间：
2022-05
影响因子：
2.4
通讯作者：
Matsura, Tatsuya
中科院分区：
文献类型：
--
作者：
Kurashiki, Tatsuyuki;Horikoshi, Yosuke;Kamizaki, Koki;Sunaguchi, Teppei;Hara, Kazushi;Morimoto, Masaki;Kitagawa, Yoshinori;Nakaso, Kazuhiro;Otsuki, Akihiro;Matsura, Tatsuya
辅酶Q10 （CoQ10）在体外和体内促进伤口愈合。然而，辅酶q10促进伤口修复的分子机制尚不清楚。在本研究中，我们通过细胞伤口愈合模型研究了辅酶q10诱导伤口修复的分子机制。CoQ10以剂量依赖的方式促进HaCaT细胞损伤后伤口愈合和伤口介导的细胞极化。与其他CoQ同源物、苯醌衍生物和聚异戊二烯基化合物的比较表明，CoQ10的整个结构是有效的伤口修复所必需的。在coq10处理的细胞中，损伤后Akt的磷酸化和Akt的质膜易位升高。CoQ10与一种磷脂酰肌醇3-激酶（PI3K）抑制剂共同处理可消除其对伤口修复的促进作用。免疫组织化学和生化分析表明，辅酶q10增加了细胞顶膜域小窝蛋白-1 （Cav-1）的定位和富膜部分Cav-1的含量。在HaCaT细胞中，Cav-1的缺失抑制coq10介导的伤口修复和PI3K/Akt信号的激活。这些结果表明，CoQ10增加Cav-1向质膜的易位，激活下游PI3K/Akt信号通路，导致HaCaT细胞的伤口闭合。
Coenzyme Q10 (CoQ10) promotes wound healing in vitro and in vivo. However, the molecular mechanisms underlying the promoting effects of CoQ10 on wound repair remain unknown. In the present study, we investigated the molecular mechanisms through which CoQ10 induces wound repair using a cellular wound-healing model. CoQ10 promoted wound closure in a dose-dependent manner and wound-mediated cell polarization after wounding in HaCaT cells. A comparison with other CoQ homologs, benzoquinone derivatives, and polyisoprenyl compounds suggested that the whole structure of CoQ10 is required for potent wound repair. The phosphorylation of Akt after wounding and the plasma membrane translocation of Akt were elevated in CoQ10-treated cells. The promoting effect of CoQ10 on wound repair was abrogated by co-treatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor. Immunohistochemical and biochemical analyses showed that CoQ10 increased the localization of caveolin-1 (Cav-1) to the apical membrane domains of the cells and the Cav-1 content in the membrane-rich fractions. Depletion of Cav-1 suppressed CoQ10-mediated wound repair and PI3K/Akt signaling activation in HaCaT cells. These results indicated that CoQ10 increases the translocation of Cav-1 to the plasma membranes, activating the downstream PI3K/Akt signaling pathway, and resulting in wound closure in HaCaT cells.
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影响因子：
3.7
作者：
Hill MM;Daud NH;Aung CS;Loo D;Martin S;Murphy S;Black DM;Barry R;Simpson F;Liu L;Pilch PF;Hancock JF;Parat MO;Parton RG
通讯作者：
Parton RG
影响因子：
2.4
作者：
Kashiba M;Terashima M;Sagawa T;Yoshimura S;Yamamoto Y
通讯作者：
Yamamoto Y
影响因子：
21.3
作者：
Kreitzer, G;Schmoranzer, J;Rodriguez-Boulan, E
通讯作者：
Rodriguez-Boulan, E
影响因子：
6.3
作者：
Blass, Sandra C.;Goost, Hans;Ellinger, Sabine
通讯作者：
Ellinger, Sabine
影响因子：
2.7
作者：
Baroni, Adone;Buommino, Elisabetta;Wolf, Ronni
通讯作者：
Wolf, Ronni