215. Placental expression of uncoupling protein-2 is reduced by glucocorticoid treatment in late pregnancy: implications for placental oxidative stress

2008 ◽  
Vol 20 (9) ◽  
pp. 15
Author(s):  
M. L. Jones ◽  
P. J. Mark ◽  
B. J. Waddell
Keyword(s):  
Oxidative Stress ◽  
Gestational Age ◽  
Uncoupling Protein ◽  
Late Pregnancy ◽  
Uncoupling Protein 2 ◽  
Dexamethasone Treatment ◽  
Glucocorticoid Treatment ◽  
Ucp2 Expression ◽  
Endogenous Protection ◽  
Placental Oxidative Stress

Placental oxidative stress plays a key role in the pathophysiology of placenta-related disorders in humans, most notably in preeclampsia (PE) and intrauterine growth restriction (IUGR). Protection from oxidative stress is provided by antioxidant enzymes including superoxide dismutase-1 and 2 (SOD-1 and –2) and catalase (CAT), which convert reactive oxygen species (ROS) to inert products. It has also been proposed that uncoupling protein-2 (UCP2) may limit oxidative stress by reducing ROS production, but little is known of UCP2 expression in placenta. Here we measured placental UCP2, SOD-1, SOD-2 and CAT mRNA expression (by qRT–PCR) in normal gestation and after glucocorticoid-induced IUGR. The latter was included because glucocorticoids can increase oxidative stress in other tissues, and placental glucocorticoid exposure is elevated in both PE and IUGR. Placentas were collected on days 16 and 22 of normal pregnancy (term = day 23) and on day 22 after dexamethasone treatment (0.75 mg/mL in drinking water from day 13). The two morphologically-distinct regions of the placenta, the junctional (JZ) and labyrinth (LZ) zones, were analysed separately because effectively all growth occurs in the LZ over this period. Expression of UCP2 in LZ exceeded that in JZ (P < 0.001) and increased in both zones between days 16 and 22 (LZ: 2.0-fold; JZ: 3.2-fold). Dexamethasone treatment reduced UCP2 in LZ (44%; P < 0.05) but not in JZ. SOD1 and SOD2 increased with gestational age in LZ (P < 0.01) and JZ (P < 0.05), but neither were affected by dexamethasone. CAT expression was higher (2.4-fold, P < 0.001) in LZ compared with JZ but did not change with gestational age or dexamethasone. In summary, these data suggest that endogenous protection against oxidative stress increases in the rat placenta during late pregnancy. Moreover, this protection may be compromised by reduced placental UCP2 expression in a model of glucocorticoid-induced IUGR.

523. PLACENTAL ANTIOXIDANT ENZYMES IN RAT PREGNANCY SHOW ZONE- AND STAGE-DEPENDENT VARIATION

2009 ◽  
Vol 21 (9) ◽  
pp. 122
Author(s):  
M. L. Jones ◽  
P. J. Mark ◽  
T. A. Mori ◽  
B. J. Waddell
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Enzymes ◽  
Oxidative Damage ◽  
Mrna Expression ◽  
Late Pregnancy ◽  
Late Gestation ◽  
Ros Generation ◽  
Dexamethasone Treatment ◽  
Endogenous Protection ◽  
Thioredoxin Reductases

Placental oxidative stress plays a key role in the pathophysiology of placenta-related disorders including preeclampsia. Protection from oxidative stress is provided by antioxidant enzymes which inactivate reactive oxygen species (ROS). The rat placenta consists of two major zones, the junctional (JZ) and labyrinth (LZ), and because only the LZ grows in late gestation we hypothesized it generates more ROS and thus requires greater antioxidant protection. Our previous studies on expression of the antioxidants superoxide dismutase (SOD)-1, SOD-2 and catalase support this hypothesis. Here, we extend these observations to include mRNA expression of SOD-3 and thioredoxin reductases (Txnrd-1, -2, -3) and activities of SOD, hydrogen peroxide (H2O2) scavenging and xanthine oxidase (XO). Placental oxidative damage was assessed by measurement of F2-isoprostanes and TBARS concentrations. We also measured the effects of maternal dexamethasone treatment, since glucocorticoid excess is known to induce oxidative damage in other tissues. Placentas were collected from untreated mothers on days 16 and 22 (term=day 23) and on day 22 after dexamethasone treatment from day 13 (1 μg/ml drinking water). SOD-3, Txnrd-1, -2, and -3 mRNAs were measured in JZ and LZ by qRT-PCR. F2-isoprostanes were measured by GC-MS and kit assays were used to measure TBARS and the activities of SOD, H2O2 scavenging and XO. In both placental zones, expression of SOD-3 and Txnrd-1 mRNAs and H2O2 scavenging activity decreased from day 16 to 22, whereas XO activity increased. Dexamethasone treatment increased H2O2 scavenging in both zones, but had no effect on SOD or XO activities or antioxidant mRNA expression. Despite predicted increases in placental ROS generation in late pregnancy and after dexamethasone, neither F2-isoprostanes nor TBARS were increased. These and our previous data suggest that endogenous protection against oxidative stress is abundant in the rat placenta and provides protection against potential oxidative insults including glucocorticoid excess.

Abstract P160: Role of Uncoupling Protein 2 in Stroke Susceptibility of Stroke-prone Spontaneously Hypertensive Rat

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Speranza Rubattu ◽  
Maria Cotugno ◽  
Franca Bianchi ◽  
Sara Di Castro ◽  
Rosita Stanzione ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Expression ◽  
Mitochondrial Dysfunction ◽  
Spontaneously Hypertensive Rat ◽  
Uncoupling Protein ◽  
Uncoupling Protein 2 ◽  
Spontaneously Hypertensive ◽  
Hypertensive Rat ◽  
Ucp2 Expression

Mitochondrial dysfunction causes severe cellular derangements potentially underlying tissue injury and consequent diseases. Evidence of a direct involvement of mitochondrial dysfunction in hypertensive target organ damage is still poor. The gene encoding Uncoupling Protein 2 (UCP2), a inner mitochondrial membrane protein, maps inside stroke QTL/STR1 in stroke prone spontaneously hypertensive rat (SHRSP). We explored the role of UCP2 in stroke pathogenesis of SHRSP. Male SHRSP, stroke resistant SHR (SHRSR) and reciprocal STR1/congenic rats were fed with stroke permissive Japanese style diet (JD). A group of SHRSP received JD plus fenofibrate (150 mg/kg/die). Rats were sacrificed at stroke occurrence. Additional SHRSR and SHRSP rats were sacrificed at 1, 3, 6, 12 months of age upon regular diet. SBP, BW, proteinuria, stroke signs were monitored. Brains were used for molecular analysis (UCP2 gene and protein expression, Nf-kB protein expression, oxidative stress quantification) and for histological analyses. As a result, brain UCP2 expression was reduced to 20% by JD only in SHRSP (showing 100% stroke occurrence by 7 weeks of JD). Fenofibrate protected SHRSP from stroke and upregulated brain UCP2 (+ 100%). Congenic rats carrying STR1/QTL showed increased (+100%) brain UCP2 expression, as compared to SHRSP, when resistant to stroke, and, viceversa, decreased (-50%) brain UCP2 levels, as compared to SHRSR, when susceptible to stroke. Brain UCP2 expression progressively decreased with aging only in SHRSP, down to 15% level at one year of age (when SHRSP showed spontaneous stroke). Both brain Nf-kB expression and oxidative stress levels increased when UCP2 expression was downregulated, and viceversa. Histological analysis showed both ischemic and haemorrhagic lesions at stroke occurrence. Our results highlight a role of UCP2 in stroke predisposition associated to hypertension in an animal model of complex human disease.

scholarly journals Exhaustive Training Increases Uncoupling Protein 2 Expression and Decreases Bcl-2/Bax Ratio in Rat Skeletal Muscle

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
W. Y. Liu ◽  
W. He ◽  
H. Li
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscles ◽  
Energy Production ◽  
Uncoupling Protein ◽  
Female Rats ◽  
Control Group ◽  
Uncoupling Protein 2 ◽  
Sprague Dawley ◽  
Ucp2 Expression ◽  
Gastrocnemius Muscles

This work investigates the effects of oxidative stress due to exhaustive training on uncoupling protein 2 (UCP2) and Bcl-2/Bax in rat skeletal muscles. A total of 18 Sprague-Dawley female rats were randomly divided into three groups: the control group (CON), the trained control group (TC), and the exhaustive trained group (ET). Malondialdehyde (MDA), superoxide dismutase (SOD), xanthine oxidase (XOD), ATPase, UCP2, and Bcl-2/Bax ratio in red gastrocnemius muscles were measured. Exhaustive training induced ROS increase in red gastrocnemius muscles, which led to a decrease in the cell antiapoptotic ability (Bcl-2/Bax ratio). An increase in UCP2 expression can reduce ROS production and affect mitochondrial energy production. Thus, oxidative stress plays a significant role in overtraining.

Ablation of uncoupling protein 2 exacerbates salt-induced cardiovascular and renal remodeling associated with enhanced oxidative stress

2014 ◽  
Vol 175 (1) ◽  
pp. 206-210 ◽  
Author(s):  
Shuangtao Ma ◽  
Yan Zhang ◽  
Qiang Wang ◽  
Dachun Yang ◽  
De Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Uncoupling Protein ◽  
Uncoupling Protein 2

Increased reactive oxygen species production with antisense oligonucleotides directed against uncoupling protein 2 in murine endothelial cells

2002 ◽  
Vol 80 (6) ◽  
pp. 757-764 ◽  
Author(s):  
Carine Duval ◽  
Anne Nègre-Salvayre ◽  
Alain Doglio ◽  
Robert Salvayre ◽  
Luc Pénicaud ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Antisense Oligonucleotides ◽  
Uncoupling Protein ◽  
Reactive Oxygen ◽  
Ldl Oxidation ◽  
Uncoupling Protein 2 ◽  
Thiobarbituric Acid Reactive Substance ◽  
Oxygen Species

Uncoupling protein 2 (UCP-2) belongs to the mitochondrial anion carrier family. It is ubiquitously expressed but is most abdundant in the reticuloendothelial system. In addition to uncoupling function, UCP-2 modulates the production of reactive oxygen species (ROS) by isolated mitochondria. Using an antisense oligonucleotide strategy, we investigated whether a defect in UCP-2 expression modulates ROS in intact endothelial cells. Murine endothelial cells (CRL 2181) pretreated by antisense oligonucleotides directed against UCP-2 mRNA exhibited a significant and specific increase in membrane potential and intracellular ROS level compared with control scrambled or anti-UCP-1 and -UCP-3 antisense oligonucleotides. These specific changes induced by UCP-2 antisense oligonucleotides were correlated with a rise in extracellular superoxide anion production and oxidative stress assessed by thiobarbituric acid reactive substance values. Taken together, these data suggest a role for UCP-2 in control of ROS production and subsequent oxidation of surrounding compounds mediating oxidative stress of endothelial cells. These data also support the notion that manipulations of UCP-2 at the genetic level could control ROS metabolism at the cellular level.Key words: UCP-2, reactive oxygen species, LDL oxidation, oxidative stress, mitochondria, endothelial cells.

scholarly journals Maternal glucocorticoid treatment modulates placental leptin and leptin receptor expression and materno-fetal leptin physiology during late pregnancy, and elicits hypertension associated with hyperleptinaemia in the early-growth-retarded adult offspring

2001 ◽  
pp. 529-539 ◽  
Author(s):  
MC Sugden ◽  
ML Langdown ◽  
MJ Munns ◽  
MJ Holness
Keyword(s):  
Body Weight ◽  
Protein Expression ◽  
Rat Model ◽  
Early Life ◽  
Leptin Receptor ◽  
Late Pregnancy ◽  
Female Offspring ◽  
Early Growth ◽  
Dexamethasone Treatment ◽  
Glucocorticoid Treatment

BACKGROUND: Leptin concentrations are increased during late pregnancy, and leptin receptors are expressed in placental and fetal tissues, suggesting a role for leptin in placental and/or fetal growth, or both. In humans, leptin concentrations in adulthood are inversely related to body weight at birth, independent of adult adiposity, and correlate with fasting insulin. Glucocorticoids and insulin regulate leptin secretion. Excessive exposure to glucocorticoids during late fetal development in the rat causes intrauterine growth retardation (IUGR), together with hypertension and hyperinsulinaemia in adulthood. Leptin may have a role in the development of some forms of hypertension. OBJECTIVE: To determine whether IUGR induced by maternal glucocorticoid treatment during the last third of pregnancy in the rat is associated with modulation of either maternal or fetal leptin concentrations, the placental expression of leptin or the short form of the leptin receptor (ObR-S), or combinations thereof, and to evaluate whether hypertension or hyperinsulinaemia in the early-growth-retarded adult progeny of dexamethasone-treated dams is associated with altered leptin concentrations. DESIGN AND METHODS: Dexamethasone was administered to pregnant rats from day 15 to day 21 of gestation via a chronically implanted subcutaneous osmotic minipump. Protein expression of leptin and ObR-S in the placenta at day 21 of pregnancy was measured by western blotting. Plasma leptin and insulin concentrations were determined by radioimmunoassay and ELISA respectively. Systolic hypertension was measured by tail cuff plethysmography. RESULTS: Dexamethasone administration during the last third of pregnancy decreased placental mass and fetal body weight at day 21 of gestation, caused maternal hyperleptinaemia but fetal hypoleptinaemia, and suppressed placental leptin protein expression whilst up-regulating placental protein expression of ObR-S. The male and female offspring of dexamethasone-treated dams were hypertensive from 12 weeks of age. One-year-old offspring of dexamethasone-treated dams exhibited significant hyperleptinaemia compared with age-matched controls, an effect associated with hyperinsulinaemia in the male, but not female, offspring. CONCLUSIONS: The rat model of maternal dexamethasone treatment is established as a paradigm of 'programmed' hypertension in man. Our data show modification of placental leptin and leptin receptor protein expression by dexamethasone treatment during the last third of pregnancy. We also show that leptin concentrations are suppressed during fetal life but increased in adulthood in this rat model of programmed hypertension. Our data do not necessarily establish a causal relationship between fetal hypoleptinaemia and impaired fetal growth during early life, or between hyperleptinaemia and hypertension in adulthood. Nevertheless, they suggest that hyperleptinaemia may be a component of the cluster of metabolic abnormalities seen in the insulin resistance syndrome in man. They also suggest that excessive fetal exposure to glucocorticoids could be a common early-life stimulus to the association between hyperinsulinaemia, hypertension and hyperleptinaemia often seen in individuals of low birthweight.

scholarly journals Klotho inhibits H 2 O 2 -induced oxidative stress and apoptosis in periodontal ligament stem cells by regulating UCP2 expression

2020 ◽  
Author(s):  
Lilei Zhu ◽  
Hui Xie ◽  
Qingqing Liu ◽  
Fei Ma ◽  
Hao Wu
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Chronic Periodontitis ◽  
Periodontal Ligament ◽  
Gingival Crevicular Fluid ◽  
Uncoupling Protein ◽  
Transmembrane Protein ◽  
Periodontal Ligament Stem Cells ◽  
Ucp2 Expression

Abstract Background Periodontitis, known as a human chronic inflammatory disease, has affected the life of millions of individuals. Known risk factors such as metabolic disease and oxidative stress have been reported to be closely associated with the initiation or development of periodontitis. However, the etiology of periodontitis remains unclear. Klotho, a single-pass transmembrane protein, has been widely reported to modulate cellular processes in various diseases. However, the role of Klotho in periodontitis is unknown.Results In this study, we designed and conducted a series of experiments to evaluate the role of Klotho in chronic periodontitis. Our experimental results showed that Klotho was downregulated in the gingival tissues, gingival crevicular fluid (GCF), and periodontal ligament stem cells (PDLSCs) of chronic periodontitis patients. Besides, Klotho upregulated the production of uncoupling protein 2 (UCP2) in H2O2-treated PDLSCs. In function, Klotho inhibited H2O2-induced oxidative stress and cellular apoptosis in PDLSCs. Moreover, the rescue assay suggested that UCP2 knock-down suppressed the effects of Klotho on H2O2-induced oxidative stress and apoptosis in PDLSCs.Conclusions In conclusion, we found that Klotho inhibits H2O2-induced oxidative stress and apoptosis in PDLSCs by regulating UCP2 expression. This novel discovery may provide a potential target for chronic periodontitis treatment.

Lopimune-induced mitochondrial toxicity is attenuated by increased uncoupling protein-2 level in treated mouse hepatocytes

2015 ◽  
Vol 468 (3) ◽  
pp. 401-407 ◽  
Author(s):  
Sara El Hoss ◽  
Georges M. Bahr ◽  
Karim S. Echtay
Keyword(s):  
Oxidative Stress ◽  
Protease Inhibitor ◽  
Regulatory Mechanism ◽  
Uncoupling Protein ◽  
Uncoupling Protein 2 ◽  
Ros Production ◽  
Mitochondrial Toxicity ◽  
Mouse Hepatocytes ◽  
Proton Leakage ◽  
Feedback Regulatory Mechanism

We have demonstrated that the antiretroviral protease inhibitor Lopimune increases oxidative stress in mouse hepatocytes and subsequently mitochondrial proton leakage. This effect is mediated by increased uncoupling protein-2 expression which in turn inhibits ROS production as a negative feedback regulatory mechanism.

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