Deficiency in gp91Phox (NOX2) Protects against Oxidative Stress and Cardiac Dysfunction in Iron Overloaded Mice

Mak, I. Tong; Kramer, Jay H.; Chmielinska, Joanna J.; Weglicki, William B.; Spurney, Christopher F.

doi:10.3390/hearts1020012

Cited by 2 publications

(2 citation statements)

References 36 publications

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“…MiR-217-5p also suppressed the PM2.5-induced up-regulation of TNF-α and IFN-γ protein expressions. Besides, the massive production of ROS can lead to the peroxidation of proteins, lipids and nucleic acids, ultimately resulting in cell injury and even death [ 22 ]. NOX is an important enzyme for the production of ROS, and inhibiting its production can relieve oxidative stress [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

MiR-217-5p inhibits smog (PM2.5)-induced inflammation and oxidative stress response of mouse lung tissues and macrophages through targeting STAT1

Xie

et al. 2022

Aging

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Objective: To explore the roles of macrophages’ miR-217-5p in the process of PM2.5 induced acute lung injury. Methods: GEO database and KEGG pathway enrichment analysis as well as GSEA were used to predicted the miRNA and associated target signals. And then mice and RAW246.7 macrophages treated with PM2.5 to imitate PM2.5 induced acute lung injury environment and then transfected with miR-217-5p NC or miR-217-5p mimic. The levels of inflammatory factors TNF-α and anti-inflammatory factor IL-10 of mice serum were tested by ELISA. And the pathological changes and ROS level of mouse lung tissues were stained by HE and DHE staining. The proteins expression of phosphorylated-STAT1, total-STAT1, TNF-α, IFN-γ as well as p47, gp91, NOX4 in mice or RAW264.7 cells were tested by western blot or immunofluorescence of RAW264.7 cell slides. Results: The results of bioinformatics analysis indicated the miR-217 as well as STAT1 were involved PM2.5 associated lung injury. After exposure to PM2.5, the decreased levels of serum TNF-α but not IL-10, consistent with reduced macrophages’ accumulation as well as decreased ROS levels in lung tissues in miR-217-5p mimic group vs miR-217-5p NC group mice, and moreover, the protein expression levels of phosphorylated--STAT1, total-STAT1, TNF-α, IFN-γ, p47, gp91 and NOX4 in mouse lung tissues and RTAW246.7 macrophages cells were all significantly reduced with miR-217-5p mimic administration. The above phenomena were reversed by specific STAT1-inhibitor HY-N8107. Conclusions: miR-217-5p suppressed the activated STAT1-signal induced inflammation and oxidative stress trigged by PM2.5 in macrophages and resulted in the decreased lung injure caused by PM2.5.

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Section: Discussionmentioning

confidence: 99%

MiR-217-5p inhibits smog (PM2.5)-induced inflammation and oxidative stress response of mouse lung tissues and macrophages through targeting STAT1

Xie

et al. 2022

Aging

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“…Nox2 has been implicated in microglia-mediated ROS production and ensuing neuronal injury and death in co-culture studies [57]. Studies in Nox2-knockout mice also demonstrate significantly decreased lipid peroxidation and oxidative stress in the setting of cellular iron accumulation [58], further implicating elevated Nox2 in iron-mediated ROS effects and ferroptosis.…”

Section: Discussionmentioning

confidence: 99%

Contemporary Antiretroviral Therapy Dysregulates Iron Transport and Augments Mitochondrial Dysfunction in HIV-Infected Human Microglia and Neural-Lineage Cells

Kaur,

Minchella,

Alvarez-Carbonell

et al. 2023

IJMS

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HIV-associated cognitive dysfunction during combination antiretroviral therapy (cART) involves mitochondrial dysfunction, but the impact of contemporary cART on chronic metabolic changes in the brain and in latent HIV infection is unclear. We interrogated mitochondrial function in a human microglia (hμglia) cell line harboring inducible HIV provirus and in SH-SY5Y cells after exposure to individual antiretroviral drugs or cART, using the MitoStress assay. cART-induced changes in protein expression, reactive oxygen species (ROS) production, mitochondrial DNA copy number, and cellular iron were also explored. Finally, we evaluated the ability of ROS scavengers or plasmid-mediated overexpression of the antioxidant iron-binding protein, Fth1, to reverse mitochondrial defects. Contemporary antiretroviral drugs, particularly bictegravir, depressed multiple facets of mitochondrial function by 20–30%, with the most pronounced effects in latently infected HIV+ hμglia and SH-SY5Y cells. Latently HIV-infected hμglia exhibited upregulated glycolysis. Increases in total and/or mitochondrial ROS, mitochondrial DNA copy number, and cellular iron accompanied mitochondrial defects in hμglia and SH-SY5Y cells. In SH-SY5Y cells, cART reduced mitochondrial iron–sulfur-cluster-containing supercomplex and subunit expression and increased Nox2 expression. Fth1 overexpression or pre-treatment with N-acetylcysteine prevented cART-induced mitochondrial dysfunction. Contemporary cART impairs mitochondrial bioenergetics in hμglia and SH-SY5Y cells, partly through cellular iron accumulation; some effects differ by HIV latency.

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Deficiency in gp91Phox (NOX2) Protects against Oxidative Stress and Cardiac Dysfunction in Iron Overloaded Mice

Cited by 2 publications

References 36 publications

MiR-217-5p inhibits smog (PM2.5)-induced inflammation and oxidative stress response of mouse lung tissues and macrophages through targeting STAT1

MiR-217-5p inhibits smog (PM2.5)-induced inflammation and oxidative stress response of mouse lung tissues and macrophages through targeting STAT1

Contemporary Antiretroviral Therapy Dysregulates Iron Transport and Augments Mitochondrial Dysfunction in HIV-Infected Human Microglia and Neural-Lineage Cells

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