Altered mitochondrial proteome and functional dynamics in patients with rheumatoid arthritis

Khanna, S. N.; Padhan, Prasanta; Jaiswal, Kumar Sagar; Jain, Ankit; Ghosh, Arup; Tripathy, Arun Kumar; Gowda, Harsha; Raghav, Sunil K.; Gupta, Bhawna

doi:10.1016/j.mito.2020.06.005

Cited by 15 publications

(18 citation statements)

References 40 publications

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“…Compared to healthy controls, peripheral blood mononuclear cells (PBMCs) from RA and fibromyalgia patients express less mETC complexes at the protein level, have reduced cellular ATP levels, and have a diminished mitochondrial membrane potential ( 105 – 107 ). Similarly, genes associated with OxPhos are downregulated in peripheral leukocytes of JIA patients in comparison with healthy children.…”

Section: Systemic and Genetic Links To Mitochondrial Alterations In R...mentioning

confidence: 99%

Mitochondria and sensory processing in inflammatory and neuropathic pain

2022

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Rheumatic diseases, such as osteoarthritis and rheumatoid arthritis, affect over 750 million people worldwide and contribute to approximately 40% of chronic pain cases. Inflammation and tissue damage contribute to pain in rheumatic diseases, but pain often persists even when inflammation/damage is resolved. Mechanisms that cause this persistent pain are still unclear. Mitochondria are essential for a myriad of cellular processes and regulate neuronal functions. Mitochondrial dysfunction has been implicated in multiple neurological disorders, but its role in sensory processing and pain in rheumatic diseases is relatively unexplored. This review provides a comprehensive understanding of how mitochondrial dysfunction connects inflammation and damage-associated pathways to neuronal sensitization and persistent pain. To provide an overall framework on how mitochondria control pain, we explored recent evidence in inflammatory and neuropathic pain conditions. Mitochondria have intrinsic quality control mechanisms to prevent functional deficits and cellular damage. We will discuss the link between neuronal activity, mitochondrial dysfunction and chronic pain. Lastly, pharmacological strategies aimed at reestablishing mitochondrial functions or boosting mitochondrial dynamics as therapeutic interventions for chronic pain are discussed. The evidence presented in this review shows that mitochondria dysfunction may play a role in rheumatic pain. The dysfunction is not restricted to neuronal cells in the peripheral and central nervous system, but also includes blood cells and cells at the joint level that may affect pain pathways indirectly. Pre-clinical and clinical data suggest that modulation of mitochondrial functions can be used to attenuate or eliminate pain, which could be beneficial for multiple rheumatic diseases.

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Section: Systemic and Genetic Links To Mitochondrial Alterations In R...mentioning

confidence: 99%

Mitochondria and sensory processing in inflammatory and neuropathic pain

2022

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“…Recent advances in proteomics provide a new opportunity to reveal the pathological mechanism of RA and the targeted proteins and networks related to drug actions. Especially, the development of the quantitative proteomic technique of isobaric tags for relative and absolute quantification (iTRAQ) with strong cation exchange (SCX)-reverse-phase liquid chromatography-tandem mass spectrometry (SCX-RPLC-MS/MS), which would be the more powerful proteomics methodologies in the pathogenesis mechanism and drug action of RA research [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Quantitative proteomic analysis of Bi Zhong Xiao decoction against collagen-induced arthritis rats in the early and late stages

Wang

Wen

et al. 2022

BMC Complement Med Ther

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Background Rheumatoid arthritis (RA) is a chronic, progressive, systemic autoimmune inflammatory disease. Bi Zhong Xiao decoction (BZXD) performs multiple functions for rheumatoid arthritis (RA) treatment for decades. In this study, we aimed to study the protein alterations of BZXD in the early and late stages of RA. Methods Sprague–Dawley rats were randomly divided into the Control, collagen-induced arthritis (CIA) and BZXD groups. Clinical assessment, paw thickness, weight changes and serum inflammatory cytokine levels were used to evaluate anti-inflammatory effects. Histopathological tests were performed to assess the improvement of inflammation and synovial hyperplasia. Moreover, we analyzed the proteins profiling of synovial tissue samples with different time intervals after BZXD treatment by Isobaric Tag for Relative Absolute (ITRAQ) quantitative proteomics technology. To further explore the interrelationships among differentially expressed proteins (DEPs), we used DAVID Bioinformatics Resources v6.8 and STRING 11.0 for bioinformatics analysis. Besides, the western blot and immunohistochemistry were exerted to verify related proteins. Results In our study, BZXD ameliorated joint inflammation, and suppressed the pathological changes in arthrosis of CIA rats. The proteomic analysis demonstrated that CIA rats were mainly involved in two significant pathways (the focal adhesion and the ECM-receptor interaction) in the early stage. BZXD down-regulated the expression of proteins involved in these pathways, such as CAV1, CHAD, COL3A1, COL5A2, COL6A1, and COL6A5. Additionally, BZXD exerts anti-inflammatory effects in the late stage mainly by increasing the expression of FASN and affecting fatty acid metabolism. Conclusion BZXD exerts therapeutic effects on RA through multi-pathways in the early and late stages. This work may provide proteomic clues for treating RA by BZXD.

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“…Proteomics refers to the large-scale, high-throughput study of the complete set of proteins expressed in a cell, tissue or species. Through proteomics technology, proteins and post-translational modification sites (such as phosphorylation) in biological samples can be identified or quantified on a large scale, and valuable information and rules can be mined from high-throughput data analysis to provide clues and a basis for the exploration of functional mechanisms (Khanna et al, 2020;Teitsma et al, 2018). Isobaric tags for relative and absolute quantification (iTRAQ) and tandem mass tags (TMT) are two proteomic labeling techniques developed in recent years (Khanna et al, 2020;Liu et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

“…Through proteomics technology, proteins and post-translational modification sites (such as phosphorylation) in biological samples can be identified or quantified on a large scale, and valuable information and rules can be mined from high-throughput data analysis to provide clues and a basis for the exploration of functional mechanisms (Khanna et al, 2020;Teitsma et al, 2018). Isobaric tags for relative and absolute quantification (iTRAQ) and tandem mass tags (TMT) are two proteomic labeling techniques developed in recent years (Khanna et al, 2020;Liu et al, 2020). Compared with iTRAQ, TMT quantitative proteomic analysis can simultaneously perform quantitative analysis of proteins in samples under 11 different conditions.…”

Section: Introductionmentioning

confidence: 99%

Anti‐rheumatoid arthritis effects of Xanthii Fructus by affecting the PI3K‐AKT signaling pathway based on TMT‐labeled quantitative proteomics

Jiang

Zhang

et al. 2022

Biomedical Chromatography

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Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic symmetrical multiple arthritis. Current traditional counter‐therapies are expensive and have side effects. Xanthii Fructus has effects in expelling wind and cold, draining the nasal orifice, and removing wind and dampness. However, its mechanism of action against rheumatoid arthritis is unknown. In this paper, the mechanism of the anti‐ rheumatoid arthritis effect of Xanthii Fructus is studied by proteomics. The experimental results show that it could significantly reduce serum inflammatory factor levels, alleviate joint edema, improve vasodilation and congestion, and significantly reduce the number of inflammatory cells. Proteomics results show that the PI3K‐AKT signaling pathway is the key pathway for Xanthii Fructus to treat rheumatoid arthritis. In this study, we obtained a new understanding of the mechanism of Xanthii Fructus in the treatment of rheumatoid arthritis, which provided a theoretical basis for its prevention and treatment and laid the foundation for further research.

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Altered mitochondrial proteome and functional dynamics in patients with rheumatoid arthritis

Cited by 15 publications

References 40 publications

Mitochondria and sensory processing in inflammatory and neuropathic pain

Mitochondria and sensory processing in inflammatory and neuropathic pain

Quantitative proteomic analysis of Bi Zhong Xiao decoction against collagen-induced arthritis rats in the early and late stages

Anti‐rheumatoid arthritis effects of Xanthii Fructus by affecting the PI3K‐AKT signaling pathway based on TMT‐labeled quantitative proteomics

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