scholarly journals Impaired Mitochondrial Function Results from Oxidative Stress in the Full-Term Placenta of Sows with Excessive Back-Fat

Animals ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 360 ◽  
Author(s):  
Liang Tian ◽  
Jiahe Huang ◽  
Aiyou Wen ◽  
Peishi Yan
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Function ◽  
Placental Tissue ◽  
Term Placenta ◽  
Mitochondrial Alterations ◽  
Transport Chain ◽  
Elevated Protein ◽  
Atp Generation ◽  
Complex I Activity

The aim of this study was to determine the effect of excessive back-fat (BF) of sows on placental oxidative stress, ATP generation, mitochondrial alterations in content and structure, and mitochondrial function in isolated trophoblasts. Placental tissue was collected by vaginal delivery from BFI (15–20 mm, n = 10) and BFII (21–27 mm, n = 10) sows formed according to BF at mating. Our results demonstrated that excessive back-fat contributed to augmented oxidative stress in term placenta, as evidenced by excessive production of ROS, elevated protein carbonylation, and reduced SOD, GSH-PX, and CAT activities (p < 0.05). Indicative of mitochondrial dysfunction, reduced mitochondrial respiration in cultured trophoblasts was linked to decreased ATP generation, lower mitochondrial Complex I activity and reduced expression of electron transport chain subunits in placenta of BFII sows (p < 0.05). Meanwhile, we observed negative alterations in mitochondrial biogenesis and structure in the placenta from BFII group (p < 0.05). Finally, our in vitro studies showed lipid-induced ROS production resulted in mitochondrial alterations in trophoblasts, and these effects were blocked by antioxidant treatment. Together, these data reveal that excessive back-fat aggravates mitochondrial injury induced by increased oxidative stress in pig term placenta, which may have detrimental consequences on placental function and therefore impaired fetal growth and development.

scholarly journals Inhibition of Mitochondrial Complex III in Candida Albicans ADH1 Deletion Mutant Attenuates Its Pathogenicity Significantly

2021 ◽  
Author(s):  
Hui Guo ◽  
Yi Shan Zhang ◽  
Yan Jun Song ◽  
Ya Jing Zhao ◽  
Shui Xiu Li ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Alternative Oxidase ◽  
Oxidase Inhibitor ◽  
Complex Iii ◽  
Ros Production ◽  
Mitochondrial Complex ◽  
Aerobic Growth ◽  
Transport Chain ◽  
Atp Generation

Abstract Fermentation and aerobic respiration in mitochondria are coordinately regulated and compensated either when C. albicans grows in vitro or in the hosts, and the creature gain the strong viability. It’s insufficient to influent the growth, reproduction and pathogenicity of C. albicans by inhibiting the electron transport chain (ECT) CI, CII, CIII, CV, or fermentation related gene ADH1. Our study showed that the induction of AA (inhibitor of complex III) rather than SHAM (alternative oxidase inhibitor) abolishes the mitochondrial function completely （96% less ATP generation, 59% reduction in MMP), and increases ROS production significantly in ADH1-deleted mutant ( adh1Δ/ adh1Δ ) that in turn becomes hypersensitive to azole and apoptosis, less viable and more difficult to form hyphae. At the same time, the expression of virulence related genes ALS3 and HWP1 were significantly lower than that of WT under AA induction. Under the induction of AA, the mitochondrial function of WT was slightly damaged and cell apoptosis increased slightly，ROS production and sensitivity of azoles increased significantly, but mycelium formation and the growth of cells were not affected. Under aerobic growth, we observed an ADH1 - dependent mitochondrial effect in C. albicans demonstrated by 64% less ATP generation, 58% reduction in MMP and significant elevations of the ROS and apoptosis in ADH1 -deleted mutant. However, mycelium formation and azole susceptibility are not affected. Our results suggested that ADH1 plus CIII played an important role in antifungal activity by damaging mitochondrial function, inhibiting cell growth and hyphae formation, promoting apoptosis and reducing pathogenicity.

scholarly journals MCART1 is required for mitochondrial NAD transport

2020 ◽  
Author(s):  
Nora Kory ◽  
Jelmi uit de Bos ◽  
Sanne van der Rijt ◽  
Nevena Jankovic ◽  
Miriam Güra ◽  
...  
Keyword(s):  
Redox Reactions ◽  
Tca Cycle ◽  
Substrate Oxidation ◽  
Isolated Mitochondria ◽  
Mitochondrial Transporter ◽  
Transport Chain ◽  
Atp Generation ◽  
Higher Eukaryotes ◽  
Complex I Activity

AbstractThe nicotinamide adenine dinucleotide (NAD+/NADH) pair is a cofactor in redox reactions and is particularly critical in mitochondria as it connects substrate oxidation by the tricarboxylic acid (TCA) cycle to ATP generation by the electron transport chain (ETC) and oxidative phosphorylation. While a mitochondrial NAD+ transporter has been identified in yeast, how NAD enters mitochondria in higher eukaryotes is unknown. Here, we mine gene essentiality data from human cell lines to identify MCART1 (SLC25A51) as co-essential with ETC components. MCART1-null cells have large decreases in TCA cycle flux, mitochondrial respiration, ETC complex I activity, and mitochondrial levels of NAD+ and NADH. Isolated mitochondria from cells lacking or overexpressing MCART1 have greatly decreased or increased NAD uptake in vitro, respectively. Moreover, MCART1 and NDT1, a yeast mitochondrial NAD+ transporter, can functionally complement for each other. Thus, we propose that MCART1 is the long sought mitochondrial transporter for NAD in human cells.

scholarly journals Glycine ameliorates mitochondrial dysfunction caused by ABT-199 in porcine oocytes

2021 ◽  
Author(s):  
Sicong Yu ◽  
Lepeng Gao ◽  
Yang Song ◽  
Xin Ma ◽  
Shuang Liang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Oocyte Maturation ◽  
Mitochondrial Function ◽  
Protective Action ◽  
Damage Model ◽  
Developmental Competence ◽  
Free Calcium ◽  
Maturation In Vitro

Abstract Mitochondria play an important role in controlling oocyte developmental competence. Our previous studies showed that glycine can regulate mitochondrial function and improve oocyte maturation in vitro. However, the mechanisms by which glycine affects mitochondrial function during oocyte maturation in vitro have not been fully investigated. In this study, we induced a mitochondrial damage model in oocytes with the Bcl-2-specific antagonist ABT-199. We investigated whether glycine could reverse the mitochondrial dysfunction induced by ABT-199 exposure and whether it is related to calcium regulation. Our results showed that ABT-199 inhibited cumulus expansion, decreased the oocyte maturation rate and the intracellular glutathione (GSH) level, caused mitochondrial dysfunction, induced oxidative stress, which was confirmed by decreased mitochondrial membrane potential (Δ⍦m) and the expression of mitochondrial function-related genes (PGC-1α), and increased reactive oxygen species (ROS) levels and the expression of apoptosis-associated genes (Bax, caspase-3, CytC). More importantly, ABT-199-treated oocytes showed an increase in the intracellular free calcium concentration ([Ca 2+]i) and had impaired cortical type 1 inositol 1,4,5-trisphosphate receptors (IP3R1) distribution. Nevertheless, treatment with glycine significantly ameliorated mitochondrial dysfunction, oxidative stress and apoptosis, glycine also regulated [Ca 2+]i levels and IP3R1 cellular distribution, which further protects oocyte maturation in ABT-199-induced porcine oocytes. Taken together, our results indicate that glycine has a protective action against ABT-199-induced mitochondrial dysfunction in porcine oocytes.

scholarly journals Phytochemicals from the Cocoa Shell Modulate Mitochondrial Function, Lipid and Glucose Metabolism in Hepatocytes via Activation of FGF21/ERK, AKT, and mTOR Pathways

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 136
Author(s):  
Miguel Rebollo-Hernanz ◽  
Yolanda Aguilera ◽  
Maria A. Martin-Cabrejas ◽  
Elvira Gonzalez de Gonzalez de Mejia
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Function ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Fatty Acid Synthase ◽  
Cell Model ◽  
Fibroblast Growth Factor 21 ◽  
Alcoholic Fatty Liver ◽  
Atp Production ◽  
Cocoa Shell

The cocoa shell is a by-product that may be revalorized as a source of bioactive compounds to prevent chronic cardiometabolic diseases. This study aimed to investigate the phytochemicals from the cocoa shell as targeted compounds for activating fibroblast growth factor 21 (FGF21) signaling and regulating non-alcoholic fatty liver disease (NAFLD)-related biomarkers linked to oxidative stress, mitochondrial function, and metabolism in hepatocytes. HepG2 cells treated with palmitic acid (PA, 500 µmol L−1) were used in an NAFLD cell model. Phytochemicals from the cocoa shell (50 µmol L−1) and an aqueous extract (CAE, 100 µg mL−1) enhanced ERK1/2 phosphorylation (1.7- to 3.3-fold) and FGF21 release (1.4- to 3.4-fold) via PPARα activation. Oxidative stress markers were reduced though Nrf-2 regulation. Mitochondrial function (mitochondrial respiration and ATP production) was protected by the PGC-1α pathway modulation. Cocoa shell phytochemicals reduced lipid accumulation (53–115%) and fatty acid synthase activity (59–93%) and prompted CPT-1 activity. Glucose uptake and glucokinase activity were enhanced, whereas glucose production and phosphoenolpyruvate carboxykinase activity were diminished. The increase in the phosphorylation of the insulin receptor, AKT, AMPKα, mTOR, and ERK1/2 conduced to the regulation of hepatic mitochondrial function and energy metabolism. For the first time, the cocoa shell phytochemicals are proved to modulate FGF21 signaling. Results demonstrate the in vitro preventive effect of the phytochemicals from the cocoa shell on NAFLD.

scholarly journals α1-Microglobulin (A1M) Protects Human Proximal Tubule Epithelial Cells from Heme-Induced Damage In Vitro

2020 ◽  
Vol 21 (16) ◽  
pp. 5825 ◽  
Author(s):  
Amanda Kristiansson ◽  
Sara Davidsson ◽  
Maria E. Johansson ◽  
Sarah Piel ◽  
Eskil Elmér ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Proximal Tubule ◽  
Mitochondrial Function ◽  
Radical Scavenging ◽  
Related Factor ◽  
Protective Effects ◽  
Cellular Expression ◽  
Human Proximal Tubule

Oxidative stress is associated with many renal disorders, both acute and chronic, and has also been described to contribute to the disease progression. Therefore, oxidative stress is a potential therapeutic target. The human antioxidant α1-microglobulin (A1M) is a plasma and tissue protein with heme-binding, radical-scavenging and reductase activities. A1M can be internalized by cells, localized to the mitochondria and protect mitochondrial function. Due to its small size, A1M is filtered from the blood into the glomeruli, and taken up by the renal tubular epithelial cells. A1M has previously been described to reduce renal damage in animal models of preeclampsia, radiotherapy and rhabdomyolysis, and is proposed as a pharmacological agent for the treatment of kidney damage. In this paper, we examined the in vitro protective effects of recombinant human A1M (rA1M) in human proximal tubule epithelial cells. Moreover, rA1M was found to protect against heme-induced cell-death both in primary cells (RPTEC) and in a cell-line (HK-2). Expression of stress-related genes was upregulated in both cell cultures in response to heme exposure, as measured by qPCR and confirmed with in situ hybridization in HK-2 cells, whereas co-treatment with rA1M counteracted the upregulation. Mitochondrial respiration, analyzed with the Seahorse extracellular flux analyzer, was compromised following exposure to heme, but preserved by co-treatment with rA1M. Finally, heme addition to RPTE cells induced an upregulation of the endogenous cellular expression of A1M, via activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)-pathway. Overall, data suggest that A1M/rA1M protects against stress-induced damage to tubule epithelial cells that, at least partly, can be attributed to maintaining mitochondrial function.

Evaluation of Mitochondrial Function in Isolated Rat Hepatocytes and Mitochondria during Oxidative Stress

2007 ◽  
Vol 35 (3) ◽  
pp. 353-361 ◽  
Author(s):  
Zuzana Červinková ◽  
Halka Lotková ◽  
Pavla Křivaková ◽  
Tomáš Roušar ◽  
Otto Kučera ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Function ◽  
Mitochondrial Permeability Transition ◽  
Energy Requirement ◽  
High Energy ◽  
Molecular Probe ◽  
Isolated Rat Hepatocytes ◽  
Isolated Mitochondria

The majority of toxic agents act either fully or partially via oxidative stress, the liver, specifically the mitochondria in hepatocytes, being the main target. Maintenance of mitochondrial function is essential for the survival and normal performance of hepatocytes, which have a high energy requirement. Therefore, greater understanding of the role of mitochondria in hepatocytes is of fundamental importance. Mitochondrial function can be analysed in several basic models: hepatocytes cultured in vitro; mitochondria in permeabilised hepatocytes; and isolated mitochondria. The aim of our study was to use all of these approaches to evaluate changes in mitochondria exposed in vitro to a potent non-specific peroxidating agent, tert-butylhydroperoxide (tBHP), which is known to induce oxidative stress. A decrease in the mitochondrial membrane potential (MMP) was observed in cultured hepatocytes treated with tBHP, as illustrated by a significant reduction in Rhodamine 123 accumulation and by a decrease in the fluorescence of the JC-1 molecular probe. Respiratory Complex I in the mitochondria of permeabilised hepatocytes showed high sensitivity to tBHP, as documented by high-resolution respirometry. This could be caused by the oxidation of NADH and NADPH by tBHP, followed by the disruption of mitochondrial calcium homeostasis, leading to the collapse of the MMP. A substantial decrease in the MMP, as determined by tetraphenylphosphonium ion-selective electrode measurements, also confirmed the dramatic impact of tBHP-induced oxidative stress on mitochondria. Swelling was observed in isolated mitochondria exposed to tBHP, which could be prevented by cyclosporin A, which is evidence for the role of mitochondrial permeability transition. Our results demonstrate that all of the above-mentioned models can be used for toxicity assessment, and the data obtained are complementary.

scholarly journals Damaging Effects of Bisphenol A on the Kidney and the Protection by Melatonin: Emerging Evidences from In Vivo and In Vitro Studies

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Anongporn Kobroob ◽  
Wachirasek Peerapanyasut ◽  
Nipon Chattipakorn ◽  
Orawan Wongmekiat
Keyword(s):  
Oxidative Stress ◽  
Bisphenol A ◽  
Mitochondrial Function ◽  
Dependent Manner ◽  
Redox Equilibrium ◽  
Membrane Potential Change ◽  
Kidney Mitochondria ◽  
Dose Dependent

This study investigates the effects of bisphenol A (BPA) contamination on the kidney and the possible protection by melatonin in experimental rats and isolated mitochondrial models. Rats exposed to BPA (50, 100, and 150 mg/kg, i.p.) for 5 weeks demonstrated renal damages as evident by increased serum urea and creatinine and decreased creatinine clearance, together with the presence of proteinuria and glomerular injuries in a dose-dependent manner. These changes were associated with increased lipid peroxidation and decreased antioxidant glutathione and superoxide dismutase. Mitochondrial dysfunction was also evident as indicated by increased reactive oxygen species production, decreased membrane potential change, and mitochondrial swelling. Coadministration of melatonin resulted in the reversal of all the changes caused by BPA. Studies using isolated mitochondria showed that BPA incubation produced dose-dependent impairment in mitochondrial function. Preincubation with melatonin was able to sustain mitochondrial function and architecture and decreases oxidative stress upon exposure to BPA. The findings indicated that BPA is capable of acting directly on the kidney mitochondria, causing mitochondrial oxidative stress, dysfunction, and subsequently, leading to whole organ damage. Emerging evidence further suggests the protective benefits of melatonin against BPA nephrotoxicity, which may be mediated, in part, by its ability to diminish oxidative stress and maintain redox equilibrium within the mitochondria.

scholarly journals Palmitate-induced toxicity is associated with impaired mitochondrial respiration and accelerated oxidative stress in cultured cardiomyocytes: the critical role of Coenzyme Q9/10

2019 ◽  
Author(s):  
Phiwayinkosi V. Dludla ◽  
Sonia Silvestri ◽  
Patrick Orlando ◽  
Sithandiwe E. Mazibuko-Mbeje ◽  
Rabia Johnson ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Mitochondrial Function ◽  
Mitochondrial Respiration ◽  
Antioxidant Activities ◽  
Critical Role ◽  
Limited Information ◽  
Transport Chain ◽  
Oxidative Stress Status ◽  
H9c2 Cardiomyocytes

AbstractImpaired mitochondrial function concomitant to enhanced oxidative stress-induced damage are well established mechanisms involved in hyperlipidemia-induced cardiotoxicity. Coenzyme Q9/10 (CoQ) is known to be a critical component of the mitochondrial electron transport chain that efficiently supports the process of bioenergetics in addition to its antioxidant activities. However, there is very limited information on the direct effect of myocardial lipid overload on endogenous CoQ levels in association with mitochondrial respiration and oxidative stress status. Here, such effects were explored by exposing H9c2 cardiomyocytes to various doses (0.15 to 1 mM) of palmitate for 24 hours. The results demonstrated that palmitate doses ≥ 0.25 mM are enough to impair mitochondrial respiration and cause oxidative stress. Although endogenous CoQ levels are enhanced by palmitate doses ≤ 5 mM, this is not enough to counteract oxidative stress, but is sufficient to maintain cell viability of cardiomyocytes, suggesting a compensation mechanism. Palmitate doses > 5 mM caused severe mitochondrial toxicity, including reduction of cell viability. Interestingly, enhancement of CoQ levels with the lowest dose of palmitate (0.15 mM) was accompanied by a significantly reduction of CoQ oxidation status, as well as low cytosolic production of reactive oxygen species. From the overall findings, it appears that CoQ response may be crucial to improve mitochondrial function and thus protect against hyperlipidemia-induced insult. These results further suggest that therapeutic agents that can stimulate endogenous levels of CoQ may be beneficial in protecting the myocardium against diabetes associated complications.

scholarly journals Hypoxia and oxidative stress induce sterile placental inflammation in vitro

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bernadette C. Baker ◽  
Alexander E. P. Heazell ◽  
Colin Sibley ◽  
Rachael Wright ◽  
Helen Bischof ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Placental Tissue ◽  
Nitrative Stress ◽  
Increased Risk ◽  
Cell Free Fetal Dna ◽  
Placental Inflammation ◽  
Inflammatory Profile ◽  
Conditioned Culture Medium ◽  
And Oxidative Stress

AbstractFetal growth restriction (FGR) and stillbirth are associated with placental dysfunction and inflammation and hypoxia, oxidative and nitrative stress are implicated in placental damage. Damage-associated molecular patterns (DAMPs) are elevated in pregnancies at increased risk of FGR and stillbirth and are associated with increase in pro-inflammatory placental cytokines. We hypothesised that placental insults lead to release of DAMPs, promoting placental inflammation. Placental tissue from uncomplicated pregnancies was exposed in vitro to hypoxia, oxidative or nitrative stress. Tissue production and release of DAMPs and cytokines was determined. Oxidative stress and hypoxia caused differential release of DAMPs including uric acid, HMGB1, S100A8, cell-free fetal DNA, S100A12 and HSP70. After oxidative stress pro-inflammatory cytokines (IL-1α, IL-1β, IL-6, IL-8, TNFα, CCL2) were increased both within explants and in conditioned culture medium. Hypoxia increased tissue IL-1α/β, IL-6, IL-8 and TNFα levels, and release of IL-1α, IL-6 and IL-8, whereas CCL2 and IL-10 were reduced. IL1 receptor antagonist (IL1Ra) treatment prevented hypoxia- and oxidative stress-induced IL-6 and IL-8 release. These findings provide evidence that relevant stressors induce a sterile inflammatory profile in placental tissue which can be partially blocked by IL1Ra suggesting this agent has translational potential to prevent placental inflammation evident in FGR and stillbirth.

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