Anti-stress effects of carnosine on restraint-evoked immunocompromise in mice through spleen lymphocyte number maintenance.
Anti-stress effects of carnosine on restraint-evoked immunocompromise in mice through spleen lymphocyte number maintenance.
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肌肽通过维持脾脏淋巴细胞数量对小鼠约束诱发的免疫功能低下的抗应激作用
DOI：
10.1371/journal.pone.0033190
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kurihara H
中科院分区：
文献类型：
--
作者：
Li YF;He RR;Tsoi B;Li XD;Li WX;Abe K;Kurihara H
肌肽(β-丙氨酰-L-组氨酸)是一种天然存在的二肽，被认为是一种神经递质，是脑组织胺的储存库，可作用于组胺能神经元系统，减轻应激所致的损伤。然而，对肌肽在应激诱导的免疫妥协中的作用的了解是有限的。结果表明，在束缚应激条件下，小鼠的脾指数和包括NK细胞在内的脾淋巴细胞数量明显下降。束缚应激可降低单个NK细胞的杀伤活性(LU10/脾)，而单个NK细胞(LU10/106细胞)的杀伤活性无明显变化。而肌肽(150 mg/kg和300 mg/kg)可增加束缚应激小鼠的脾指数和脾淋巴细胞(包括NK细胞)数量，并提高每只小鼠脾NK细胞的细胞毒活性。这些结果表明，肌肽通过维持脾淋巴细胞数量而改善应激诱导的免疫损伤。进一步发现，肌肽可以降低应激引起的血浆皮质酮水平的升高。另一方面，肌肽和糖皮质激素受体拮抗剂RU486治疗可阻止应激小鼠脾淋巴细胞线粒体膜电位降低和线粒体细胞色素c释放，增加Bcl2/Bax mRNA比值，减少末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记(TUNEL)阳性细胞。以上结果提示，肌肽维持脾淋巴细胞数量与抑制糖皮质激素溢出所致淋巴细胞凋亡有关。肌肽对淋巴细胞增殖的刺激作用也有助于维持应激小鼠脾淋巴细胞数量。鉴于组胺水平升高，肌肽对束缚诱导的免疫妥协的抗应激作用可能是通过肌肽-组胺代谢途径实现的。综上所述，肌肽通过抑制淋巴细胞凋亡和刺激淋巴细胞增殖来维持小鼠脾淋巴细胞数量，从而防止束缚应激小鼠的免疫妥协。
Carnosine (β-alanyl-L-histidine), a naturally occurring dipeptide, has been characterized as a putative neurotransmitter and serves as a reservoir for brain histamine, which could act on histaminergic neurons system to relieve stress-induced damages. However, understanding of the role of carnosine in stress-evoked immunocompromise is limited. In this study, results showed that when mice were subjected to restraint stress, spleen index and the number of spleen lymphocytes including Natural Killer (NK) cells were obviously decreased. Results also demonstrated that restraint stress decreased the cytotoxic activity of NK cells per spleen (LU10/spleen) while the activity of a single NK cell (LU10/106 cells) was not changed. However, oral administration of carnosine (150 and 300 mg/kg) increased spleen index and number of spleen lymphocytes (including NK cells), and elevated the cytotoxic activity of NK cells per spleen in restraint-stressed mice. These results indicated that carnosine ameliorated stress-evoked immunocompromise through spleen lymphocyte number maintenance. Carnosine was further found to reduce stress-induced elevation of plasma corticosterone level. On the other hand, results showed that carnosine and RU486 (a glucocorticoids receptor antagonist) treatment prevented the reduction in mitochondrion membrane potential and the release of mitochondrial cytochrome c into cytoplasm, increased Bcl-2/Bax mRNA ratio, as well as decreased terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells in spleen lymphocytes of stressed mice. The results above suggested that the maintenance of spleen lymphocyte number by carnosine was related with the inhibition of lymphocytes apoptosis caused by glucocorticoids overflow. The stimulation of lymphocyte proliferation by carnosine also contributed to the maintenance of spleen lymphocyte number in stressed mice. In view of the elevated histamine level, the anti-stress effects of carnosine on restraint-evoked immunocompromise might be via carnosine-histamine metabolic pathway. Taken together, carnosine maintained spleen lymphocyte number by inhibiting lymphocyte apoptosis and stimulating lymphocyte proliferation, thus prevented immunocompromise in restraint-stressed mice.
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影响因子：
7.7
作者：
Janssen, B;Hohenadel, D;van der Woude, FJ
通讯作者：
van der Woude, FJ
影响因子：
6.1
作者：
Kurihara, H;Koda, H;Tanaka, T
通讯作者：
Tanaka, T
DOI：
10.1152/ajplung.00283.2006
发表时间：
2007-05-01
影响因子：
4.9
作者：
Cuzzocrea, Salvatore;Genovese, Tiziana;Vancheri, Carlo
通讯作者：
Vancheri, Carlo
影响因子：
7.5
作者：
Ito, C
通讯作者：
Ito, C
影响因子：
2.9
作者：
Kozan, Ramazan;Sefil, Fatih;Bagirici, Faruk
通讯作者：
Bagirici, Faruk