Rat uncoupling protein 2 (UCP2): Expression in obese ventromedial hypothalamus (VMH)-lesioned animals

1998 ◽  
Vol 22 (11) ◽  
pp. 1121-1126 ◽  
Author(s):  
A Strobel ◽  
M Combettes-Souverain ◽  
L Doaré ◽  
AD Strosberg ◽  
T Issad
Keyword(s):  
Uncoupling Protein ◽  
Ventromedial Hypothalamus ◽  
Uncoupling Protein 2 ◽  
Ucp2 Expression

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.

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 Uncoupling Protein 2 Regulates Palmitic Acid-Induced Hepatoma Cell Autophagy

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Jiaxin Lou ◽  
Yunjiao Wang ◽  
Xuejiang Wang ◽  
Ying Jiang
Keyword(s):  
Palmitic Acid ◽  
Uncoupling Protein ◽  
Hepatoma Cell ◽  
Atp Synthesis ◽  
Hepatoma Cells ◽  
Uncoupling Protein 2 ◽  
Ros Production ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Ucp2 Expression

Mitochondrial uncoupling protein 2 (UCP2) is suggested to have a role in the development of nonalcoholic steatohepatitis (NASH). However, the mechanism remains unclear. Autophagy is an important mediator of many pathological responses. This study aims to investigate the relationship between UCP2 and hepatoma cells autophagy in palmitic acid- (PA-) induced lipotoxicity. H4IIE cells were treated with palmitic acid (PA), and cell autophagy and apoptosis were examined. UCP2 expression, in association with LC3-II and caspase-3, which are indicators of cell autophagy and apoptosis, respectively,was measured. Results demonstrated that UCP2 was associated with autophagy during PA-induced hepatic carcinoma cells injury. Tests on reactive oxygen species (ROS) showed that UCP2 overexpression strongly decreases PA-induced ROS production and apoptosis. Conversely, UCP2 inhibition by genipin or UCP2 mRNA silencing enhances PA-induced ROS production and apoptosis. Autophagy partially participates in this progress. Moreover, UCP2 was associated with ATP synthesis during PA-induced autophagy. In conclusion, increasing UCP2 expression in hepatoma cells may contribute to cell autophagy and antiapoptotic as result of fatty acid injury. Our results may bring new insights for potential NASH therapies.

scholarly journals Mitochondrial uncoupling protein-2 deficiency protects steatotic mouse hepatocytes from hypoxia/reoxygenation

2012 ◽  
Vol 302 (3) ◽  
pp. G336-G342 ◽  
Author(s):  
Zachary P. Evans ◽  
Arun P. Palanisamy ◽  
Alton G. Sutter ◽  
Justin D. Ellett ◽  
Venkat K. Ramshesh ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Uncoupling Protein ◽  
Thiobarbituric Acid ◽  
Atp Depletion ◽  
Uncoupling Protein 2 ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Ucp2 Expression ◽  
Hypoxia Reoxygenation

Steatotic livers are sensitive to ischemic events and associated ATP depletion. Hepatocellular necrosis following these events may result from mitochondrial uncoupling protein-2 (UCP2) expression. To test this hypothesis, we developed a model of in vitro steatosis using primary hepatocytes from wild-type (WT) and UCP2 knockout (KO) mice and subjected them to hypoxia/reoxygenation (H/R). Using cultured hepatocytes treated with emulsified fatty acids for 24 h, generating a steatotic phenotype (i.e., microvesicular and broad-spectrum fatty acid accumulation), we found that the phenotype of the WT and UCP2 KO were the same; however, cellular viability was increased in the steatotic KO hepatocytes following 4 h of hypoxia and 24 h of reoxygenation; Hepatocellular ATP levels decreased during hypoxia and recovered after reoxygenation in the control and UCP2 KO steatotic hepatocytes but not in the WT steatotic hepatocytes; mitochondrial membrane potential in WT and UCP2 KO steatotic groups was less than control groups but higher than UCP2 KO hepatocytes. Following reoxygenation, lipid peroxidation, as measured by thiobarbituric acid reactive substances, increased in all groups but to a greater extent in the steatotic hepatocytes, regardless of UCP2 expression. These results demonstrate that UCP2 sensitizes steatotic hepatocytes to H/R through mitochondrial depolarization and ATP depletion but not lipid peroxidation.

scholarly journals Inhibition of Uncoupling Protein 2 Attenuates Cardiac Hypertrophy Induced by Transverse Aortic Constriction in Mice

2015 ◽  
Vol 36 (5) ◽  
pp. 1688-1698 ◽  
Author(s):  
Xiao-Bing Ji ◽  
Xiu-Rong Li ◽  
Hao-Ding ◽  
Qi Sun ◽  
Yang Zhou ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Cardiac Hypertrophy ◽  
Uncoupling Protein ◽  
Pressure Overload ◽  
Left Ventricular ◽  
Uncoupling Protein 2 ◽  
Transverse Aortic Constriction ◽  
Aortic Constriction ◽  
Atp Concentration ◽  
Ucp2 Expression

Background: Uncoupling protein 2 (UCP2) is critical in regulating energy metabolism. Due to the significant change in energy metabolism of myocardium upon pressure overload, we hypothesize that UCP2 could contribute to the etiology of cardiac hypertrophy. Methods: Adult male C57BL/6J mice were subjected to pressure overload by using transverse aortic constriction (TAC), and then received genipin (a UCP2 selective inhibitor; 25 mg/kg/d, ip) or vehicle for three weeks prior to histologic assessment of myocardial hypertrophy. ATP concentration, ROS level, and myocardial apoptosis were also examined. A parallel set of experiments was also conducted in UCP2-/- mice. Results: TAC induced left ventricular hypertrophy, as reflected by increased ventricular weight/thickness and increased size of myocardial cell (vs. sham controls). ATP concentration was decreased; ROS level was increased. Apoptosis and fibrosis markers were increased. TAC increased mitochondrial UCP2 expression in the myocardium at both mRNA and protein levels. Genipin treatment attenuated cardiac hypertrophy and the histologic/biochemical changes described above. Hypertrophy and associated changes induced by TAC in UCP2-/- mice were much less pronounced than in WT mice. Conclusions: Blocking UCP2 expression attenuates cardiac hypertrophy induced by pressure overload.

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.

scholarly journals Endogenous islet uncoupling protein-2 expression and loss of glucose homeostasis in ob/ob mice

2006 ◽  
Vol 190 (3) ◽  
pp. 659-667 ◽  
Author(s):  
Monique C Saleh ◽  
Michael B Wheeler ◽  
Catherine B Chan
Keyword(s):  
Insulin Secretion ◽  
Blood Glucose ◽  
Glucose Homeostasis ◽  
Uncoupling Protein ◽  
Isolated Islets ◽  
Oral Glucose ◽  
Uncoupling Protein 2 ◽  
Short Term ◽  
Ucp2 Expression

We hypothesized that the loss of glucose homeostasis in ob/ob mice is associated with upregulation of islet uncoupling protein-2 (UCP2) expression, leading to impaired glucose-stimulated insulin secretion (GSIS). Changes in glucose homeostasis in lean and ob/ob mice from 5 to 16 weeks were assessed by fasting blood glucose, plasma insulin, oral glucose tolerance, and tissue insulin sensitivity. In vitro GSIS and ATP content were assayed in isolated islets, while UCP2 expression was determined by quantitative real-time PCR and immunoblotting. Short-term reduction of UCP2 expression was achieved through transfection of islets with specific small interfering RNA. Insulin resistance was detected in 5-week-old ob/ob mice, but GSIS and blood glucose levels remained normal. By 8 weeks of age, ob/ob mice displayed fasting hyperglycemia, hyperinsulinemia and glucose intolerance, and also had elevated non-esterified fatty acid concentration in plasma. In vitro, GSIS and ATP generation were impaired in ob/ob islets. Islet UCP2 expression was elevated at 5 and 8 weeks of age. Short-term knockdown of islet UCP2 increased GSIS in islets of lean mice, but had no effect in islets from ob/ob mice. Loss of glucose homeostasis and impairment of insulin secretion from isolated islets at 8 weeks in ob/ob mice is preceded by an increase in UCP2 expression in islets. Moreover, the glucolipotoxic conditions observed are predicted to increase UCP2 activity, contributing to lower islet ATP and GSIS.

scholarly journals Uncoupling Protein 2 as a pathogenic determinant and therapeutic target in cardiovascular and metabolic diseases

2021 ◽  
Vol 19 ◽  
Author(s):  
Rosita Stanzione ◽  
Maurizio Forte ◽  
Maria Cotugno ◽  
Franca Bianchi ◽  
Simona Marchitti ◽  
...  
Keyword(s):  
Mitochondrial Membrane ◽  
Metabolic Disorders ◽  
Uncoupling Protein ◽  
Heart Diseases ◽  
Mitochondrial Protein ◽  
Uncoupling Protein 2 ◽  
Obesity And Diabetes ◽  
Ucp2 Expression ◽  
Increased Risk ◽  
Wide Range

: Uncoupling protein 2 (UCP2) is a mitochondrial protein that acts as an anion carrier. It is involved in the regulation of several processes including mitochondrial membrane potential, generation of reactive oxygen species within the inner mitochondrial membrane and calcium homeostasis. UCP2 expression can be regulated at different levels: genetic (gene variants), transcriptional [by peroxisome proliferator-activated receptors (PPARs) and microRNAs], and post-translational. Experimental evidence indicates that activation of UCP2 expression through the AMPK/PPAR-α axis exerts a protective effect toward renal damage and stroke occurrence in an animal model of ischemic stroke (IS) associated with hypertension. UCP2 plays a key role in heart diseases (myocardial infarction and cardiac hypertrophy) and metabolic disorders (obesity and diabetes). In humans, UCP2 genetic variants (-866G/A and Ala55Val) associate with an increased risk of type 2 diabetes mellitus and of IS development. Over the last few years, many agents that modulate UCP2 expression have been identified. Some of them are natural compounds of plant origin such as Brassica oleracea, curcumin, berberine and resveratrol. Other molecules, currently used in clinical practice, include anti-diabetic (gliptin) and chemotherapeutic (doxorubicin and taxol) drugs. This evidence highlights the relevant role of UCP2 for the treatment of a wide range of diseases, which affect the national health systems of the Western countries. We will review current knowledge on the physiological and pathological implications of UCP2 with particular regard to cardiovascular and metabolic disorders and will focus on the available therapeutic approaches affecting UCP2 level for the treatment of human diseases.

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