Effect of hyperhomocysteinemia on a murine model of smoke-induced pulmonary emphysema.
Effect of hyperhomocysteinemia on a murine model of smoke-induced pulmonary emphysema.
复制标题
高层半胱氨酸血症对烟雾诱导的肺肺气肿模型的影响。
DOI：
10.1038/s41598-022-16767-2
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发表时间：
2022-07-28
影响因子：
4.6
通讯作者：
Shibata, Yoko
中科院分区：
文献类型：
--
作者：
Nakano, Hiroshi;Inoue, Sumito;Minegishi, Yukihiro;Igarashi, Akira;Tokairin, Yoshikane;Yamauchi, Keiko;Kimura, Tomomi;Nishiwaki, Michiko;Nemoto, Takako;Otaki, Yoichiro;Sato, Masamichi;Sato, Kento;Machida, Hiroyoshi;Yang, Sujeong;Murano, Hiroaki;Watanabe, Masafumi;Shibata, Yoko
据报道，高同型半胱氨酸血症可增强内质网（ER）应激和随后的细胞凋亡。然而，吸烟易感性与高同型半胱氨酸血症相关的确切机制尚未完全阐明。本研究包括7至9周龄的C57BL6雄性小鼠诱导高同型半胱氨酸血症，并暴露于香烟烟雾（CS）。用同型半胱氨酸（homocysteine，Hcy）诱导人肺泡上皮细胞株A549细胞，并将其暴露于香烟烟雾提取物（CSE）中，观察细胞活力及内质网应激相关蛋白的表达。CS暴露6个月后，高同型半胱氨酸血症组肺气肿发生率明显高于对照组。随着同型半胱氨酸浓度的增加，A549细胞凋亡率增加，CSE可增强A549细胞凋亡率。ER应激标志物的蛋白表达水平在同时刺激后显著增加。值得注意的是，维生素B12和叶酸补充改善ER应激后，同时刺激A549细胞。在这项研究中，我们发现，高同型半胱氨酸血症加重CS刺激诱导的肺气肿小鼠，这表明高同型半胱氨酸血症和CS刺激增强ER应激和随后诱导的肺泡上皮细胞凋亡。提示同型半胱氨酸与CS之间存在协同作用。
Hyperhomocysteinemia was reported to enhance endoplasmic reticulum (ER) stress and subsequent apoptosis in several cells. However, the precise mechanisms of smoking susceptibility associated with hyperhomocysteinemia has not been fully elucidated. This study included 7- to 9-week-old C57BL6 male mice induced with hyperhomocysteinemia and were exposed to cigarette smoke (CS). A549 cells (human alveolar epithelial cell line) were cultured with homocysteine and were exposed to cigarette smoke extract (CSE) to observe cell viability and expression of proteins related to the ER stress. After 6 months of CS exposure, pulmonary emphysema was more severely induced in the group under the condition of hyperhomocysteinemia compared to that in the control group. The apoptotic A549 cells increased as homocysteine concentration increased and that was enhanced by CSE. Protein expression levels of ER stress markers were significantly increased after simultaneous stimulation. Notably, vitamin B12 and folate supplementation improved ER stress after simultaneous stimulation of A549 cells. In this study, we showed that hyperhomocysteinemia exacerbates CS exposure-induced emphysema in mice, suggesting that hyperhomocysteinemia and CS stimulation enhance ER stress and subsequent induced apoptosis in alveolar epithelial cells. It was suggested that there is a synergistic effect between homocysteine and CS.
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DOI：
10.2183/pjab.91.469
发表时间：
2015
期刊：
Proceedings of the Japan Academy. Series B, Physical and biological sciences
影响因子：
--
作者：
Mori K
通讯作者：
Mori K
影响因子：
9.2
作者：
Aida Y;Shibata Y;Abe S;Inoue S;Kimura T;Igarashi A;Yamauchi K;Nunomiya K;Kishi H;Nemoto T;Sato M;Sato-Nishiwaki M;Nakano H;Sato K;Kubota I
通讯作者：
Kubota I
影响因子：
3.7
作者：
Shibata Y;Inoue S;Igarashi A;Yamauchi K;Abe S;Aida Y;Nunomiya K;Sato M;Nakano H;Sato K;Watanabe T;Konta T;Ueno Y;Kato T;Kayama T;Kubota I
通讯作者：
Kubota I
DOI：
10.1165/rcmb.2006-0248oc
发表时间：
2007-04-01
影响因子：
6.4
作者：
Machiya, Jun-ichi;Shibata, Yoko;Kubota, Isao
通讯作者：
Kubota, Isao
吸烟减少高血压患者肾功能恶化可能是由同型半胱氨酸升高介导的
影响因子：
--
作者：
Huang F;Chen J;Liu X;Han F;Cai Q;Peng G;Zhang K;Chen W;Wang J;Huang H
通讯作者：
Huang H