Chenodeoxycholic acid (CDCA) treate Human hepatocellular carcinoma (HepG2) cells

News

Yourlocation： Home > News > Chenodeoxycholic acid (CDCA) treate Human hepatocellular carcinoma (HepG2) cells

Methods: Human hepatocellular carcinoma (HepG2) cells were treated with Chenodeoxycholic Acid (CDCA) ± ω3PUFA. Activation of PPARα was evaluated, and expression of PPARα, farnesoid X receptor, liver X receptor alpha (LXRα), and retinoid X receptor mRNA was evaluated by reverse-transcriptase PCR. Some results: PPARα activation was increased in HepG2 cells treated with ω3PUFA, and decreased in the presence of CDCA when compared with untreated cells. PPARα mRNA was reduced by 67% with Chenodeoxycholic Acid and restored to the level of control with ω3PUFA. LXRα mRNA increased twofold with Chenodeoxycholic Acid treatment and was significantly reduced by ω3PUFA.
Expression of PPARα, as well as LXRα mRNA levels, was reduced with Chenodeoxycholic Acid treatment and restored with the addition of ω3PUFA. These results suggest that PPARα and LXRα may be mediators by which ω3PUFA attenuate bile acid-induced hepatocellular injury. Background: Omega-3 long-chain polyunsaturated fatty acids (ω3PUFA) have been shown to be antiinflammatory in the attenuation of hepatocellular injury. Peroxisome proliferator-activated receptor alpha (PPARα) is a nuclear receptor transcription factor that inhibits the activation of nuclear factor κB, thereby repressing inflammation, and ωPUFA are PPARα ligands. The purpose of this study was to determine if ω3PUFA attenuate bile acid-induced apoptosis via PPARα.
Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disease caused by a deficiency in sterol 27-hydroxylase (CYP27A1), a key enzyme in the synthesis of Chenodeoxycholic Acid (CDCA), a primary bile acid. Deficiency of CYP27A1 and a lack of Chenodeoxycholic Acid leads to the accumulation of cholesterol and cholestanol [1]. Typical clinical manifestations of CTX include bilateral cataracts and diarrhea in childhood [2] and progressive neurologic dysfunction (cerebral ataxia, paresis, dementia, low intelligence, and psychiatric disorder), tendon xanthoma, and atherosclerosis in adolescence and early adulthood [3]. Brain magnetic resonance imaging (MRI) typically reveals symmetrical lesions in the cerebellar white matter; however, white matter lesion restricted to the spinal cord are rare.