Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to elucidate the role of peroxisome proliferator-activated receptor (PPAR)-alpha in the development of inflammation after ischemia/reperfusion injury of the kidney. We have evaluated the effects of ischemia/reperfusion on renal dysfunction, injury, and inflammation in wild-type mice or mice in which the gene for PPAR-alpha has been deleted [PPAR-alpha(-/-)] and then treated with the PPAR-alpha agonist fenofibrate. Mice were subjected to bilateral renal ischemia (30 min) and reperfusion (24 h) and received fenofibrate (3 mg/kg i.p.) before reperfusion. Plasma creatinine, urea, and aspartate aminotransferase were all used as indicators of renal dysfunction and injury. Kidneys were used for histological and immunohistochemical analysis and markers of inflammation. Fenofibrate significantly attenuated the degree of renal dysfunction, injury, and inflammation caused by ischemia/reperfusion injury. The degree of renal dysfunction, injury, and inflammation caused by ischemia/reperfusion was also significantly augmented in PPAR-alpha(-/-) mice compared with their wild-type littermates. It is interesting that fenofibrate did not protect PPAR-alpha(-/-) mice against ischemia/reperfusion injury. Therefore, we propose that ligands of PPAR-alpha may be useful in the treatment of renal ischemia/reperfusion injury and that endogenous PPAR-alpha limits the degree of renal dysfunction, injury, and inflammation associated with ischemia/reperfusion injury.
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PMID:Peroxisome proliferator-activated receptor-alpha contributes to the resolution of inflammation after renal ischemia/reperfusion injury. 1899 58

Period 2 (Per2) is a key component of the core clock oscillator and is involved in regulating a number of different biological processes and pathways. Here we report that Per2 plays a protective role in carbon tetrachloride (CCl(4))-induced hepatotoxicity via the modulation of uncoupling protein-2 (Ucp2) gene expression in mice. Hepatic injury after acute CCl(4) injection was monitored in both wild-type and Per2-null mice. At the 12-hour time point after CCl(4) treatment, many more vacuolations were observed in the liver tissues of Per2-null mice whereas fatty tissue degeneration primarily occurred in the liver tissues of wide-type mice. Serum alanine and aspartate aminotransferase activities were elevated in Per2-null mice compared with wide-type mice at 24 hours after CCl(4) treatment, which was in agreement with the observation of significantly larger areas of centrilobular necrosis in the livers of Per2-null mice. A deficit of the Per2 gene enhanced Ucp2 gene expression levels in the liver. As a consequence, intracellular levels of ATP markedly decreased in the liver, allowing increased production of toxic CCl(4) derivatives. The absence of Per2 expression caused a dramatic elevation of Clock expression and influenced Ucp2 through a mechanism that involved a Clock-controlled PPAR-alpha signal transduction pathway. Our studies suggest that the Per2 gene functions in hepatocyte protection from chemical toxicants via the regulation of hepatic Ucp2 gene expression levels.
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PMID:The protective role of Per2 against carbon tetrachloride-induced hepatotoxicity. 1905 52

We investigated the influence of the flavonoid-rich fraction from Spermacoce hispida seed (S-Frf) on PPAR-alpha gene expression, plasma and erythrocyte antioxidants status, protein metabolism, and marker enzymes in diabetic hyperlipidemic rats. Hyperlipidemia was induced by feeding a 20% high fat diet (HFD) to male albino Wistar rats for 66 days. Diabetes was induced on the 17th day by a single i.p. injection of streptozotocin (50 mg/kg). When compared with diabetic hyperlipid-emic rats, plasma TBARS and LOOH levels decreased, the activities of enzymic antioxidants (SOD, CAT, GPx) and plasma GSH levels increased in the S-Frf fed group. The activities of plasma hepatic markers serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, and levels of plasma urea, uric acid, creatinine, globulin, A/G ratio significantly decreased, whereas liver weight, total protein, and albumin increased. Oral administration of S-Frf up-regulates PPAR-alpha (peroxisome proliferator activated receptor alpha) gene expression, activates fatty acid catabolism, and is involved in the control of lipoprotein assembly in liver. The results show that S-Frf has an antihyperlipidemic effect, improves antioxidant status, and alleviates liver and kidney damage associated with HFD-fed-STZ rats by up-regulating PPAR-alpha mRNA.
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PMID:Influence of flavonoid-rich fraction from Spermacoce hispida seed on PPAR-alpha gene expression, antioxidant redox status, protein metabolism and marker enzymes in high-fat-diet fed STZ diabetic rats. 1966 17

The metabolic disorders that predispose patients to NASH (non-alcoholic steatohepatitis) include insulin resistance and obesity. Repeated hypoxic events, such as occur in obstructive sleep apnoea syndrome, have been designated as a risk factor in the progression of liver disease in such patients, but the mechanism is unclear, in particular the role of hypoxia. Therefore we studied the influence of hypoxia on the development and progression of steatohepatitis in an experimental mouse model. Mice with a hepatocellular-specific deficiency in the Pten (phosphatase and tensin homologue deleted on chromosome 10) gene, a tumour suppressor, were exposed to a 10% O2 (hypoxic) or 21% O2 (control) atmosphere for 7 days. Haematocrit, AST (aspartate aminotransferase), glucose, triacylglycerols (triglycerides) and insulin tolerance were measured in blood. Histological lesions were quantified. Expression of genes involved in lipogenesis and mitochondrial beta-oxidation, as well as FOXO1 (forkhead box O1), hepcidin and CYP2E1 (cytochrome P450 2E1), were analysed by quantitative PCR. In the animals exposed to hypoxia, the haematocrit increased (60+/-3% compared with 50+/-2% in controls; P<0.01) and the ratio of liver weight/body weight increased (5.4+/-0.2% compared with 4.7+/-0.3% in the controls; P<0.01). Furthermore, in animals exposed to hypoxia, steatosis was more pronounced (P<0.01), and the NAS [NAFLD (non-alcoholic fatty liver disease) activity score] (8.3+/-2.4 compared with 2.3+/-10.7 in controls; P<0.01), serum AST, triacylglycerols and glucose were higher. Insulin sensitivity decreased in mice exposed to hypoxia relative to controls. The expression of the lipogenic genes SREBP-1c (sterol-regulatory-element-binding protein-1c), PPAR-gamma (peroxisome-proliferator-activated receptor-gamma), ACC1 (acetyl-CoA carboxylase 1) and ACC2 (acetyl-CoA carboxylase 2) increased significantly in mice exposed to hypoxia, whereas mitochondria beta-oxidation genes [PPAR-alpha (peroxisome-proliferator-activated receptor-alpha) and CPT-1 (carnitine palmitoyltransferase-1)] decreased significantly. In conclusion, the findings of the present study demonstrate that hypoxia alone aggravates and accelerates the progression of NASH by up-regulating the expression of lipogenic genes, by down-regulating genes involved in lipid metabolism and by decreasing insulin sensitivity.
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PMID:Hypoxia aggravates non-alcoholic steatohepatitis in mice lacking hepatocellular PTEN. 1983 98