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

IF 2.2 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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引用次数: 0

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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来源期刊

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.