Extracellular Redox Regulation of Intracellular Reactive Oxygen Generation, Mitochondrial Function and Lipid Turnover in Cultured Human Adipocytes

Adhesions frequently occur postoperatively, causing morbidity. In this noninterventional observational cohort study, we enrolled patients who presented for repeat abdominal surgery, after a history of previous abdominal myomectomy, from March 1998 to June 20210 at St. Vincent’s Catholic Medical Centers. The primary outcome of this pilot study was to compare adhesion rates, extent, and severity in patients who were treated with intraperitoneal triamcinolone acetonide during the initial abdominal myomectomy (n = 31) with those who did not receive any antiadhesion interventions (n = 21), as documented on retrospective chart review. Adhesions were blindly scored using a standard scoring system. About 32% of patients were found to have adhesions in the triamcinolone group compared to 71% in the untreated group (p < 0.01). Compared to controls, adhesions were significantly less in number (0.71 vs. 2.09, p < 0.005), severity (0.54 vs. 1.38, p < 0.004), and extent (0.45 vs. 1.28, p < 0.003). To understand the molecular mechanisms, human fibroblasts were incubated in hypoxic conditions and treated with triamcinolone or vehicle. In vitro studies showed that triamcinolone directly prevents the surge of reactive oxygen species triggered by 2% hypoxia and prevents the increase in TGF-β1 that leads to the irreversible conversion of fibroblasts to an adhesion phenotype. Triamcinolone prevents the increase in reactive oxygen species through alterations in mitochondrial function that are HIF-1α-independent. Controlling mitochondrial function may thus allow for adhesion-free surgery and reduced postoperative complications.

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Cell type-specific differences in redox regulation and proliferation after low UVA doses

10.1101/425793 ◽

2018 ◽

Author(s):

Sylwia Ciesielska ◽

Patryk Bil ◽

Karolina Gajda ◽

Aleksandra Poterala-Hejmo ◽

Dorota Hudy ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Redox Regulation ◽

Cellular Proliferation ◽

Reactive Oxygen ◽

Oxygen Species ◽

Cell Type ◽

Redox Systems ◽

Human Colon Cancer ◽

Cellular Redox ◽

Hct116 Cells

AbstractUltraviolet A (UVA) radiation is harmful for living organisms but in low doses may stimulate cell proliferation. Our aim was to examine the relationships between exposure to different low UVA doses, cellular proliferation, and changes in cellular reactive oxygen species levels. In human colon cancer (HCT116) and melanoma (Me45) cells exposed to UVA doses comparable to environmental, the highest doses (30-50 kJ/m2) reduced clonogenic potential but some lower doses (1 and 10 kJ/m2) induced proliferation. This effect was cell type and dose specific. In both cell lines the levels of reactive oxygen species and nitric oxide fluctuated with dynamics which were influenced differently by UVA; in Me45 cells decreased proliferation accompanied the changes in the dynamics of H2O2 while in HCT116 cells those of superoxide. Genes coding for proteins engaged in redox systems were expressed differently in each cell line; transcripts for thioredoxin, peroxiredoxin and glutathione peroxidase showed higher expression in HCT116 cells whereas those for glutathione transferases and copper chaperone were more abundant in Me45 cells. We conclude that these two cell types utilize different pathways for regulating their redox status. Many mechanisms engaged in maintaining cellular redox balance have been described. Here we show that the different cellular responses to a stimulus such as a specific dose of UVA may be consequences of the use of different redox control pathways. Assays of superoxide and hydrogen peroxide level changes after exposure to UVA may clarify mechanisms of cellular redox regulation and help in understanding responses to stressing factors.

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Reactive oxygen species oxidize STING and suppress interferon production

eLife ◽

10.7554/elife.57837 ◽

2020 ◽

Vol 9 ◽

Author(s):

Lili Tao ◽

Andrew Lemoff ◽

Guoxun Wang ◽

Christina Zarek ◽

Alexandria Lowe ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Redox Regulation ◽

Reactive Oxygen ◽

Interferon Response ◽

Cellular Respiration ◽

Type I ◽

Oxygen Species ◽

Interferon Production ◽

Dna Sensing ◽

Cytoplasmic Dna

Reactive oxygen species (ROS) are by-products of cellular respiration that can promote oxidative stress and damage cellular proteins and lipids. One canonical role of ROS is to defend the cell against invading bacterial and viral pathogens. Curiously, some viruses, including herpesviruses, thrive despite the induction of ROS, suggesting that ROS are beneficial for the virus. However, the underlying mechanisms remain unclear. Here, we found that ROS impaired interferon response during murine herpesvirus infection and that the inhibition occurred downstream of cytoplasmic DNA sensing. We further demonstrated that ROS suppressed the type I interferon response by oxidizing Cysteine 147 on murine stimulator of interferon genes (STING), an ER-associated protein that mediates interferon response after cytoplasmic DNA sensing. This inhibited STING polymerization and activation of downstream signaling events. These data indicate that redox regulation of Cysteine 147 of mouse STING, which is equivalent to Cysteine 148 of human STING, controls interferon production. Together, our findings reveal that ROS orchestrates anti-viral immune responses, which can be exploited by viruses to evade cellular defenses.

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Contrasting influence of peplomycin and azelastine hydrochloride (Azeptin) on reactive oxygen generation in polymorphonuclear leukocytes, cytokine generation in lymphocytes, and collagen synthesis in fibroblasts

Cancer Chemotherapy and Pharmacology ◽

10.1007/bf00686553 ◽

1995 ◽

Vol 35 (3) ◽

pp. 230-236 ◽

Cited By ~ 6

Author(s):

Eisaku Ueta ◽

Tokio Osaki ◽

Kazunori Yoneda ◽

Tetsuya Yamamoto

Keyword(s):

Polymorphonuclear Leukocytes ◽

Collagen Synthesis ◽

Reactive Oxygen ◽

Oxygen Generation

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Prohibitin-1 maintains the angiogenic capacity of endothelial cells by regulating mitochondrial function and senescence

The Journal of Cell Biology ◽

10.1083/jcb.200706072 ◽

2008 ◽

Vol 180 (1) ◽

pp. 101-112 ◽

Cited By ~ 132

Author(s):

Michael Schleicher ◽

Benjamin R. Shepherd ◽

Yajaira Suarez ◽

Carlos Fernandez-Hernando ◽

Jun Yu ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Endothelial Cells ◽

Mitochondrial Function ◽

Vascular System ◽

Reactive Oxygen ◽

Direct Consequence ◽

Oxygen Species ◽

Inner Mitochondrial Membrane ◽

Prohibitin 1

Prohibitin 1 (PHB1) is a highly conserved protein that is mainly localized to the inner mitochondrial membrane and has been implicated in regulating mitochondrial function in yeast. Because mitochondria are emerging as an important regulator of vascular homeostasis, we examined PHB1 function in endothelial cells. PHB1 is highly expressed in the vascular system and knockdown of PHB1 in endothelial cells increases mitochondrial production of reactive oxygen species via inhibition of complex I, which results in cellular senescence. As a direct consequence, both Akt and Rac1 are hyperactivated, leading to cytoskeletal rearrangements and decreased endothelial cell motility, e.g., migration and tube formation. This is also reflected in an in vivo angiogenesis assay, where silencing of PHB1 blocks the formation of functional blood vessels. Collectively, our results provide evidence that PHB1 is important for mitochondrial function and prevents reactive oxygen species–induced senescence and thereby maintains the angiogenic capacity of endothelial cells.

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Reduced Mitochondrial Content, Elevated Reactive Oxygen Species, and Modulation by Denervation in Skeletal Muscle of Prefrail or Frail Elderly Women

The Journals of Gerontology Series A ◽

10.1093/gerona/glz066 ◽

2019 ◽

Vol 74 (12) ◽

pp. 1887-1895 ◽

Cited By ~ 6

Author(s):

Vita Sonjak ◽

Kathryn J Jacob ◽

Sally Spendiff ◽

Madhusudanarao Vuda ◽

Anna Perez ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Skeletal Muscle ◽

Mitochondrial Function ◽

Frail Elderly ◽

Elderly Women ◽

Reactive Oxygen ◽

Oxygen Species ◽

Respiratory Capacity ◽

Species Response ◽

Mitochondrial Impairment

Abstract Denervation and mitochondrial impairment are implicated in age-related skeletal muscle atrophy and may play a role in physical frailty. We recently showed that denervation modulates muscle mitochondrial function in octogenarian men, but this has not been examined in elderly women. On this basis, we tested the hypothesis that denervation plays a modulating role in mitochondrial impairment in skeletal muscle from prefrail or frail elderly (FE) women. Mitochondrial respiratory capacity and reactive oxygen species emission were examined in permeabilized myofibers obtained from vastus lateralis muscle biopsies from FE and young inactive women. Muscle respiratory capacity was reduced in proportion to a reduction in a mitochondrial marker protein in FE, and mitochondrial reactive oxygen species emission was elevated in FE versus young inactive group. Consistent with a significant accumulation of neural cell adhesion molecule-positive muscle fibers in FE (indicative of denervation), a 50% reduction in reactive oxygen species production after pharmacologically inhibiting the denervation-mediated reactive oxygen species response in FE women suggests a significant modulation of mitochondrial function by denervation. In conclusion, our data support the hypothesis that denervation plays a modulating role in skeletal muscle mitochondrial function in FE women, suggesting therapeutic strategies in advanced age should focus on the causes and treatment of denervation.

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