Mitochonic acid 5 regulates mitofusin 2 to protect microglia

Tan, Jian; Chen, Shuangxi; Lei, Qingyun; Yi, Shanqing; Wu, Na; Wang, Yilin; Xiao, Zijian; Wu, Honglu

doi:10.4103/1673-5374.306094

Cited by 11 publications

(2 citation statements)

References 77 publications

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“…Western blot analysis was performed according to previous studies (Chen et al., 2015; Chen et al., 2020a; Chen et al., 2020b; Jiang et al., 2016; Li et al., 2017; Tan et al., 2021; Yi et al., 2021). The tissue lysates mixed with a sample loading buffer was heated at 95˚C for 15 min.…”

Section: Methodsmentioning

confidence: 99%

Tryptophan in the diet ameliorates motor deficits in a rotenone‐induced rat Parkinson's disease model via activating the aromatic hydrocarbon receptor pathway

et al. 2021

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Background and purpose: Parkinson's disease (PD), a common neurodegenerative disorder with motor and nonmotor symptoms, does not have effective treatments.Dietary tryptophan (Trp) supplementation has potential benefits for the treatment of multiple disorders. However, whether additional Trp in the diet could be beneficial for PD remains to beinvestigated. In the present study, the neuroprotective role of dietary Trp on a rotenone-induced rat model of PD was determined. Methods:The rotenone was injected to build the PD model, and then the rats were treated with Trp in the diet. And then, an open field test, western blot analysis, and enzyme linked immunosorbent assay (ELISA) were performed. Results:We observed that dietary Trp significantly ameliorated impaired motor function, upregulated tyrosine hydroxylase expression, inhibited the nuclear transport of Nuclear factor-kappa B (NF-κB) in substantia nigra (SN), and downregulated the protein levels of IL-1β, IL-6, and TNF-α in serum in rotenone-treated rats. However, these patterns were reversed in response to treatment with ampicillin, an agent that can clean intestinal Trp metabolism flora. Moreover, after using CH223191, an inhibitor of the aromatic hydrocarbon receptor (AhR) pathway, dietary Trp could not exert neuroprotective roles in the rotenone-induced rat model of PD. Conclusion:These results suggest that Trp in the diet can protect against rotenoneinduced neurotoxicity to ameliorate motor deficits, which may be mediated through activating AhR pathway. K E Y W O R D Saromatic hydrocarbon receptor pathway, dietary tryptophan, Parkinson's disease INTRODUCTIONParkinson's disease (PD) is the second most common neurodegenerative disease, and is increasingly receiving attention from multipleThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Section: Methodsmentioning

confidence: 99%

Tryptophan in the diet ameliorates motor deficits in a rotenone‐induced rat Parkinson's disease model via activating the aromatic hydrocarbon receptor pathway

et al. 2021

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“…MA-5, a derivative of the plant hormone indole-3-acetic acid, acts as an accelerator, enhancing ATP synthesis [19,21], and it also has a cell-protective effect on microglia [33]. In this study, the addition of 10 nM MA-5 to a semen extender significantly improved sperm motility.…”

Section: Discussionmentioning

confidence: 58%

Mitochonic Acid 5 Increases Ram Sperm Quality by Improving Mitochondrial Function during Storage at 4 °C

Wang,

Liu,

Min

et al. 2024

Animals

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Semen preservation involves lengthening sperm’s fertile lifespan without any detrimental effects on its biochemical, functional, and ultrastructural properties. Liquid storage at 4 °C is a ram sperm preservation method. However, this method of storage causes irreversible damage due to cold shocks, osmotic stresses, oxidative stresses, and reductions in sperm metabolism. The present study aims to investigate whether the supplementation of mitochonic acid 5 (MA-5) in a sperm extender could improve chilled ram sperm quality and elucidate its mechanism of action. Ram sperm were diluted with a tris-citrate-glucose extender containing different concentrations of MA-5 (0, 0.1, 1, 10, and 100 nM) and stored at 4 °C for up to 48 h. Sperm motility, membrane integrity, acrosome integrity, mitochondrial membrane potential, reactive oxygen species (ROS) level, ATP content, and the expression of NADPH dehydrogenase subunits 1 (MT-ND1) and NADPH dehydrogenase subunits 6 (MT-ND6) were evaluated. It was observed that compared to the control, the 10 nM MA-5 treatment significantly (p < 0.05) increased total motility (82 ± 3.5% vs. 76 ± 5.9%), progressive motility (67.6 ± 8.2% vs. 51 ± 8.3%), and other parameters (straight-line velocity (VSL), average path velocity (VAP), and curvilinear velocity (VCL)). In addition, 10 nM MA-5 supplementation also improved ram sperm membrane integrity and acrosomal integrity as well increased mitochondrial membrane potential (51.1 ± 0.7% vs. 37.7 ± 1.3%), reduced ROS levels, and elevated adenosine triphosphate (ATP) contents. Furthermore, a Western blot analysis demonstrated that the addition of MA-5 significantly (p < 0.05) increased the expression of MT-ND1 and MT-ND6 proteins in ram sperm, with the 10 nM MA-5 treatment resulting in the highest expression level. These results suggest that MA-5 improves ram sperm quality by maintaining high sperm mitochondrial function during liquid storage at 4 °C.

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High Throughput Confined Migration Microfluidic Device for Drug Screening

Yang

Zhou

et al. 2023

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Cancer metastasis is the major cause of cancer‐related death. Excessive extracellular matrix deposition and increased stiffness are typical features of solid tumors, creating confined spaces for tumor cell migration and metastasis. Confined migration is involved in all metastasis steps. However, confined and unconfined migration inhibitors are different and drugs available to inhibit confined migration are rare. The main challenges are the modeling of confined migration, the suffering of low throughput, and others. Microfluidic device has the advantage to reduce reagent consumption and enhance throughput. Here, a microfluidic chip that can achieve multi‐function drug screening against the collective migration of cancer cells under confined environment is designed. This device is applied to screen out effective drugs on confined migration among a novel mechanoreceptors compound library (166 compounds) in hepatocellular carcinoma, non‐small lung cancer, breast cancer, and pancreatic ductal adenocarcinoma cells. Three compounds that can significantly inhibit confined migration in pan‐cancer: mitochonic acid 5 (MA‐5), SB‐705498, and diphenyleneiodonium chloride are found. Finally, it is elucidated that these drugs targeted mitochondria, actin polymerization, and cell viability, respectively. In sum, a high‐throughput microfluidic platform for screening drugs targeting confined migration is established and three novel inhibitors of confined migration in multiple cancer types are identified.

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Mitochonic acid 5 regulates mitofusin 2 to protect microglia

Cited by 11 publications

References 77 publications

Tryptophan in the diet ameliorates motor deficits in a rotenone‐induced rat Parkinson's disease model via activating the aromatic hydrocarbon receptor pathway

Tryptophan in the diet ameliorates motor deficits in a rotenone‐induced rat Parkinson's disease model via activating the aromatic hydrocarbon receptor pathway

Mitochonic Acid 5 Increases Ram Sperm Quality by Improving Mitochondrial Function during Storage at 4 °C

High Throughput Confined Migration Microfluidic Device for Drug Screening

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