Involvement of nitric oxide/cyclic GMP signaling pathway in the regulation of fatty acid metabolism in rat hepatocytes

2003 ◽  
Vol 65 (5) ◽  
pp. 807-812 ◽  
Author(s):  
Javier Garcı́a-Villafranca ◽  
Alberto Guillén ◽  
José Castro
2021 ◽  
Author(s):  
Yuanyuan An ◽  
Hua Duan

Abstract Introduction: Dysregulation of fatty acid metabolism often occurs in tumor, which mainly constitutes of fatty acid synthesis and oxidation. In recent years, studies found that fatty acid metabolism participated in regulation of tumor immune microenvironment, which further influenced the progress of cancer. Thus, it is important to explore the key fatty acid metabolism-related molecules, which not only affects the prognosis of ovarian cancer, but also shows a close correlation with immune microenvironment of cancer.Methods: Database from TCGA was used to explore the fatty acid metabolism-related molecules, which correlated with the prognosis of ovarian cancer using univariate and multivariate cox proportional regression model. Nomogram was constructed to predict the prognostic probability based on ACSM3 and clinicopathological parameters. GDSC database was used to investigate the chemosensitivity of ovarian cancer cells. The correlation between ACSM3 and immune status of ovarian cancer was analyzed by TIMER and TISIDB online tools. In addition, CCK8 assay was used to investigate the chemosensitivity of ovarian cancer cells, real time-PCR and western blot were used to investigate the expression of chemoresistance-related genes.Results: ACSM3 worked as an independent favorable prognostic molecule through univariate and multivariate cox regression analysis. For the use in clinical, nomogram was constructed, and higher expression of ACSM3 showed better prognosis. We found that ACSM3 could regulate PI3K/AKT signaling, and GDSC database showed that PI3K/AKT inhibitor could promote the chemosensitivity of ovarian cancer cells. In addition, the expression of ACSM3 showed significantly correlated with the immune status of ovarian cancer. In vitro experiments showed that ACSM3 can promote the chemosensitivity of ovarian cancer cells by inhibiting PI3K/AKT signaling pathway.Conclusion: Our results showed that ACSM3 acted as a favorable prognostic-related biomarker for ovarian cancer, which could promote chemosensitivity of ovarian cancer through inhibiting PI3K/AKT signaling pathway. This might be due to participate in regulating immune status of ovarian cancer microenvironment.


2013 ◽  
Vol 6 (256) ◽  
pp. rs1-rs1 ◽  
Author(s):  
P.-T. Doulias ◽  
M. Tenopoulou ◽  
J. L. Greene ◽  
K. Raju ◽  
H. Ischiropoulos

1988 ◽  
Vol 253 (1) ◽  
pp. 161-167 ◽  
Author(s):  
P Gerondaes ◽  
K G M M Alberti ◽  
L Agius

The direct effects of clofibrate analogues on carnitine acyltransferase activities and fatty acid metabolism were studied in cultured hepatocytes. Rat hepatocytes cultured with bezafibrate or ciprofibrate (0.1-10 micrograms/ml) for 48 h had increased activities of carnitine acetyltransferase (CAT; 4-6-fold) and carnitine palmitoyltransferase (CPT; 12-34%). The increase in CAT was higher in hepatocytes from the periportal zone (440%) of rat liver compared with cells from the perivenous zone (266%). In human hepatocytes, in contrast with rat, the fibrates did not cause a marked increase in CAT activity. The effects of fibrates on palmitate metabolism were dependent on the carnitine status. In the presence of exogenous carnitine (1 mM), rat hepatocytes cultured with bezafibrate had higher rates of total palmitate metabolism (29-34%) without increased partitioning of palmitate towards beta-oxidation, relative to control cultures. At low endogenous carnitine concentrations, cells cultured with bezafibrate had a greater increase in palmitate metabolism, esterification and cellular accumulation of triacylglycerol compared with the corresponding increases in the presence of carnitine. The changes in palmitate metabolism at either high or low carnitine concentrations were small in comparison with the changes in CAT activity. It is concluded that the increase in hepatic carnitine that occurs in vivo after fibrate feeding probably plays the major role in the changes in partitioning of fatty acid between beta-oxidation and esterification.


1984 ◽  
Vol 217 (2) ◽  
pp. 461-469 ◽  
Author(s):  
A D Pollard ◽  
D N Brindley

The effects of vasopressin on the short-term control of fatty acid metabolism were studied in isolated rat hepatocytes. Vasopressin increased the oxidation of oleate to CO2 and decreased the formation of ketones in hepatocytes from Wistar rats, but not from Brattleboro rats. Incubation with vasopressin for 30 min increased the conversion of oleate into triacylglycerol by 17% and 32% in hepatocytes from Wistar and Brattleboro rats respectively. The corresponding increases for the phospholipid fraction were 19% and 42%. When Wistar-rat hepatocytes were incubated with corticosterone for 6 h there was a 19% increase in triacylglycerol synthesis, and a 52% increase if vasopressin was added 30 min before the end of the incubation. Glycerol phosphate acyltransferase activity was not significantly increased by vasopressin. Incubation for 5-60 min with vasopressin increased the Vmax. of phosphatidate phosphohydrolase by 48% and 32% respectively in hepatocytes from Wistar and Brattleboro rats. These increases were antagonized if EGTA was added to the medium used for incubating the hepatocytes. The replacement of vasopressin by 5 microM-ionophore A23187 produced a significant increase of 13% in the phosphohydrolase activity. It is therefore likely that the effects of vasopressin on the phosphohydrolase are mediated by Ca2+. These results are discussed in relation to the possible function of phosphatidate phosphohydrolase in controlling the turnover of phosphoinositides, the synthesis of phosphatidylethanolamine, phosphatidylcholine and triacylglycerol, and the secretion of very-low-density lipoproteins.


Sign in / Sign up

Export Citation Format

Share Document