Protein carbonyl content: a novel biomarker for aging in HIV/AIDS patients

Kolgiri, Vaishali; Patil, Vinayak W.

doi:10.1016/j.bjid.2016.09.007

Cited by 21 publications

(11 citation statements)

References 28 publications

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“…Diabetic nephropathy (DN) is a common disease that occurs in approximately 30% of type 2 diabetic patients [1]. DN is mainly characterized by mesangial proliferation, glomerular basement membrane thickening, and podocyte loss [2,3].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-451 inhibits inflammation and proliferation of glomerular mesangial cells through down-regulating PSMD11 and NF-κB p65

Hua

et al. 2019

Bioscience Reports

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The present study aimed to investigate the regulatory roles of microRNA-451 (miR-451) on the inflammation and proliferation of glomerular mesangial cells (GMCs) under high-glucose condition, and reveal the potential mechanisms related to 26S proteasome non-ATPase regulatory subunit 11 (PSMD11) and nuclear factor-κ B (NF-κB) signaling. The interaction between PSMD11 and miR-451 was identified by dual luciferase reporter (DLR) gene assay. GMCs were treated with 5.6 mmol/l (normal, L-GMCs) and 30 mmol/l glucose (high-glucose, H-GMCs), respectively. After transfecting with pcDNA3.1-PSMD11 and/or miR-451 mimics, the expression of miR-451, PSMD11, inhibitor of NF-κB α (IκBα), phosphorylated IκBα (p-IκBα), NF-κB p65, COX-2, and cyclinD1 were detected in H-GMCs by quantitative real-time PCR (qRT-PCR) and/or Western blot. The levels of interleukin (IL)-1β, IL-6, and IL-8, cell cycle, and viability was detected by enzyme-linked immunosorbent assay, flow cytometry, and MTT assay, respectively. MiR-451 was up-regulated in H-GMCs, and negatively regulated its target PSMD11 (P<0.05). H-GMCs exhibited significantly higher levels of IL-1β, IL-6, and IL-8, cell viability, and p-IκBα, NF-κB, COX-2, and cyclinD1 expression than L-GMCs (P<0.05). The transfection of miR-451 mimics significantly decreased the levels of IL-1β, IL-6, and IL-8, inhibited the cell viability via blocking cells in G0/G1 phase, and down-regulated p-IκBα, NF-κB p65, COX-2, and cyclinD1 in H-GMCs (P<0.05). The regulatory effects of miR-451 mimics on H-GMCs were reversed by the transfection of PSMD11 (P<0.05). The up-regulation of miR-451 inhibits the inflammation and proliferation of H-GMCs through down-regulating PSMD11 and NF-κB p65.

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Section: Introductionmentioning

confidence: 99%

MicroRNA-451 inhibits inflammation and proliferation of glomerular mesangial cells through down-regulating PSMD11 and NF-κB p65

Hua

et al. 2019

Bioscience Reports

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“…Our results suggest a potential therapeutic benefit of DMF treatment in persons living with HIV, as oxidative stress in the periphery and the CNS are common features of HIV infection [4,20,36,68,70,71,[99][100][101][102]. The DMF-treated macaques used in this study were severely immune-deficient (secondary to CD8 + T lymphocyte depletion) with high SIV loads, and DMF treatment showed no apparent adverse effects above those attributable to SIV infection.…”

Section: Discussionmentioning

confidence: 64%

Dimethyl Fumarate, an Approved Multiple Sclerosis Treatment, Reduces Brain Oxidative Stress in SIV-Infected Rhesus Macaques: Potential Therapeutic Repurposing for HIV Neuroprotection

García-Mesa

Vance

et al. 2021

Antioxidants

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Dimethyl fumarate (DMF), an antioxidant/anti-inflammatory drug approved for the treatment of multiple sclerosis, induces antioxidant enzymes, in part through transcriptional upregulation. We hypothesized that DMF administration to simian immunodeficiency virus (SIV)-infected rhesus macaques would induce antioxidant enzyme expression and reduce oxidative injury and inflammation throughout the brain. Nine SIV-infected, CD8+-T-lymphocyte-depleted rhesus macaques were studied. Five received oral DMF prior to the SIV infection and through to the necropsy day. Protein expression was analyzed in 11 brain regions, as well as the thymus, liver, and spleen, using Western blot and immunohistochemistry for antioxidant, inflammatory, and neuronal proteins. Additionally, oxidative stress was determined in brain sections using immunohistochemistry (8-OHdG, 3NT) and optical redox imaging of oxidized flavoproteins containing flavin adenine dinucleotide (Fp) and reduced nicotinamide adenine dinucleotide (NADH). The DMF treatment was associated with no changes in virus replication; higher expressions of the antioxidant enzymes NQO1, GPX1, and HO-1 in the brain and PRDX1 and HO-2 in the spleen; lower levels of 8-OHdG and 3NT; a lower optical redox ratio. The DMF treatment was also associated with increased expressions of cell-adhesion molecules (VCAM-1, ICAM-1) and no changes in HLA-DR, CD68, GFAP, NFL, or synaptic proteins. The concordantly increased brain antioxidant enzyme expressions and reduced oxidative stress in DMF-treated SIV-infected macaques suggest that DMF could limit oxidative stress throughout the brain through effective induction of the endogenous antioxidant response. We propose that DMF could potentially induce neuroprotective brain responses in persons living with HIV.

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“…Increased oxidative genomic (DNA) damage has been reported in younger PWH < 60 years [ 45 ], and has been linked to accelerated aging [ 17 , 46 ] and cognitive impairment [ 47 ]. Mechanisms contributing to genomic damage are unclear, and interventions lacking.…”

Section: Discussionmentioning

confidence: 99%

Supplementing Glycine and N-acetylcysteine (GlyNAC) in Aging HIV Patients Improves Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Endothelial Dysfunction, Insulin Resistance, Genotoxicity, Strength, and Cognition: Results of an Open-Label Clinical Trial

Kumar

Suliburk

et al. 2020

Biomedicines

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Background: Patients with HIV (PWH) develop geriatric comorbidities, including functional and cognitive decline at a younger age. However, contributing mechanisms are unclear and interventions are lacking. We hypothesized that deficiency of the antioxidant protein glutathione (GSH) contributes to multiple defects representing premature aging in PWH, and that these defects could be improved by supplementing the GSH precursors glycine and N-acetylcysteine (GlyNAC). Methods: We conducted an open label clinical trial where eight PWH and eight matched uninfected-controls were studied at baseline. PWH were studied again 12-weeks after receiving GlyNAC, and 8-weeks after stopping GlyNAC. Controls did not receive supplementation. Outcome measures included red-blood cell and muscle GSH concentrations, mitochondrial function, mitophagy and autophagy, oxidative stress, inflammation, endothelial function, genomic damage, insulin resistance, glucose production, muscle-protein breakdown rates, body composition, physical function and cognition. Results: PWH had significant defects in measured outcomes, which improved with GlyNAC supplementation. However, benefits receded after stopping GlyNAC. Conclusions: This open label trial finds that PWH have premature aging based on multiple biological and functional defects, and identifies novel mechanistic explanations for cognitive and physical decline. Nutritional supplementation with GlyNAC improves comorbidities suggestive of premature aging in PWH including functional and cognitive decline, and warrants additional investigation.

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Protein carbonyl content: a novel biomarker for aging in HIV/AIDS patients

Abstract: Carbonyl content may has a role as a biomarker for detecting oxidative DNA damage induced ART toxicity and/or accelerated aging in HIV/AIDS patients. Larger studies are warranted to elucidate the role of carbonyl content as a biomarker for premature aging in HIV/AIDS patients.

Cited by 21 publications

References 28 publications

MicroRNA-451 inhibits inflammation and proliferation of glomerular mesangial cells through down-regulating PSMD11 and NF-κB p65

MicroRNA-451 inhibits inflammation and proliferation of glomerular mesangial cells through down-regulating PSMD11 and NF-κB p65

Dimethyl Fumarate, an Approved Multiple Sclerosis Treatment, Reduces Brain Oxidative Stress in SIV-Infected Rhesus Macaques: Potential Therapeutic Repurposing for HIV Neuroprotection

Supplementing Glycine and N-acetylcysteine (GlyNAC) in Aging HIV Patients Improves Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Endothelial Dysfunction, Insulin Resistance, Genotoxicity, Strength, and Cognition: Results of an Open-Label Clinical Trial

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