Sodium ferrous citrate in 5-Aminolevulinic acid supplements suppresses the effector function of feline lymphocytes by reducing the mitochondrial membrane potential

IF 1.8 3区 农林科学 Q1 VETERINARY SCIENCES Research in veterinary science Pub Date : 2025-02-28 DOI:10.1016/j.rvsc.2025.105603
Shoma Nishibori , Aika Chijiwa , Satoshi Kambayashi , Nao Iwatani , Aki Sakai , Keishiro Isayama , Yoichi Mizukami , Nobuyuki Shiranaga , Takuya Mizuno , Masaya Igase
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Abstract

5-Aminolevulinic acid (5-ALA) is an endogenous amino acid in mammalian cells; it is the first amino acid in the heme biosynthesis pathway occurring in the mitochondria. 5-ALA with sodium ferrous citrate (SFC) possesses anti-inflammatory properties by inducing heme oxygenase (HO)-1 expression and releasing heme metabolites in humans and mice. Supplements containing 5-ALA and divalent iron is available in veterinary medicine. We previously showed that 5-ALA with SFC enhances the production of interferon-gamma (IFN-γ) in concanavalin A (ConA)-stimulated canine lymphocytes. However, the effects of 5-ALA/SFC on feline lymphocytes remain to be investigated. This study demonstrated that 5-ALA/SFC-induced HO-1 expression and decreased IFN-γ production in ConA-stimulated feline lymphocytes. Comprehensive RNA sequencing analysis revealed that the activating transcription factor 4 (ATF4) signaling pathway was inhibited by adding 5-ALA/SFC. Moreover, we confirmed that 5-ALA/SFC decreased ATF4 protein expression. Furthermore, separate analyses of the effects of 5-ALA and SFC on feline lymphocytes revealed that SFC, but not 5-ALA, induced AKT dephosphorylation and mitochondrial dysfunction in activated lymphocytes. Thus, SFC in 5-ALA supplements may suppress the effector function of feline lymphocytes via mitochondrial metabolism, thereby representing a novel mechanism in 5-ALA/SFC research.
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5-氨基乙酰丙酸中的柠檬酸亚铁钠通过降低线粒体膜电位抑制猫淋巴细胞的效应功能
5-氨基乙酰丙酸(5-ALA)是哺乳动物细胞中的内源性氨基酸;它是线粒体中发生的血红素生物合成途径中的第一个氨基酸。5-ALA与柠檬酸亚铁钠(SFC)通过诱导血红素加氧酶(HO)-1表达和释放血红素代谢物在人和小鼠体内具有抗炎作用。含有5-ALA和二价铁的补充剂在兽药中是可用的。我们之前的研究表明,5-ALA与SFC可以增强ConA刺激的犬淋巴细胞中干扰素γ (IFN-γ)的产生。然而,5-ALA/SFC对猫淋巴细胞的影响仍有待研究。本研究表明,5-ALA/ sfc诱导cona刺激的猫淋巴细胞HO-1表达和IFN-γ产生减少。综合RNA测序分析发现,加入5-ALA/SFC后,激活转录因子4 (ATF4)信号通路受到抑制。此外,我们证实5-ALA/SFC降低了ATF4蛋白的表达。此外,对5-ALA和SFC对猫淋巴细胞影响的单独分析显示,SFC而不是5-ALA诱导活化淋巴细胞中AKT去磷酸化和线粒体功能障碍。因此,5-ALA补充剂中的SFC可能通过线粒体代谢抑制猫淋巴细胞的效应功能,从而代表了5-ALA/SFC研究的新机制。
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来源期刊
Research in veterinary science
Research in veterinary science 农林科学-兽医学
CiteScore
4.40
自引率
4.20%
发文量
312
审稿时长
75 days
期刊介绍: Research in Veterinary Science is an International multi-disciplinary journal publishing original articles, reviews and short communications of a high scientific and ethical standard in all aspects of veterinary and biomedical research. The primary aim of the journal is to inform veterinary and biomedical scientists of significant advances in veterinary and related research through prompt publication and dissemination. Secondly, the journal aims to provide a general multi-disciplinary forum for discussion and debate of news and issues concerning veterinary science. Thirdly, to promote the dissemination of knowledge to a broader range of professions, globally. High quality papers on all species of animals are considered, particularly those considered to be of high scientific importance and originality, and with interdisciplinary interest. The journal encourages papers providing results that have clear implications for understanding disease pathogenesis and for the development of control measures or treatments, as well as those dealing with a comparative biomedical approach, which represents a substantial improvement to animal and human health. Studies without a robust scientific hypothesis or that are preliminary, or of weak originality, as well as negative results, are not appropriate for the journal. Furthermore, observational approaches, case studies or field reports lacking an advancement in general knowledge do not fall within the scope of the journal.
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