mRNA levels of hepcidin, hemojuvelin, DMT1 and fer-roportin-1 were measured by the real-time PCR method. We examined the mRNA expression of DMT1, Ferroportin-1, trans-ferrin receptors and ferritin
on differentiated Caco2 cells grown with NASH patients’ serum in transwells. Activity of iron regulatory protein (IRP) on these cells was also analyzed by elec-trophoresis mobility www.selleckchem.com/products/chir-99021-ct99021-hcl.html shift assay (EMSA). Results: Absorption of iron from the gastrointestinal tract, the DMT1 mRNA levels of the duodenal mucosa, serum Hepcidin concentrations and Hepcidin mRNA levels of the liver and Hemojuvelin mRNA expression of the liver significantly increased in NASH patients, when compared with healthy subjects. The DMT1 mRNA levels of the Caco2 monolayer cultured with NASH patients’ serum significantly increased. N-acetylcysteine SCH727965 research buy or IRP-1 siRNA clearly inhibited the increment of DMT1 mRNA levels. EMSA showed the activation of IRP on Caco2 cells grown with NASH patients’ serum. Conclusion: In patients with NASH, increased iron absorption from the gastrointestinal tract causes hepatic iron accumulation, resulting in hepatic oxidative damage. Humoral factor(s) which induce oxidative stress in NASH serum may upregulate DMT1 expression in small intestine through the activation of IRP-1. Disclosures: The following
people have nothing to disclose: Koji Miyanishi, Toshifumi Hoki, Shingo Tanaka, Yutaka Kawano, Masayoshi Kobune, Kohichi Takada, Tsutomu Sato, Yasushi Sato, Rishu Takimoto, Junji Kato Alcohol induced liver disease (ALD) is a major health concern of alcohol abuse and a leading cause of liver-related morbidity
and mortality. The pathogenesis of ALD is multifactorial and still ill characterized. Endoplasmic reticulum (ER) stress has emerged as an important player in alcohol-induced steatosis and liver injury. Alcohol-mediated hyperhomocysteinemia (Hcy) is considered a key mechanism in alcohol-induced ER stress and recent evidence described the correlation between Hcy and liver injury in mouse strains sensitive to ALD. Acid sphin-gomyelinase (ASMase) promotes hepatocellular apoptosis and liver fibrosis, and has been shown to play a key role in oral this website alcohol-induced ER stress independently of Hcy. However, the degree of Hcy differs between oral alcohol feeding and the intragastric alcohol infusion model, being significantly lower in the former, thus raising the possibility for a threshold phenomenon for Hcy to induce ER stress regardless of ASMase. To test this hypothesis, ASMase null mice were subjected to alcohol feeding using the intrasgastric infusion model to examine their susceptibility to steatosis, liver injury, inflammation, mitochon-drial cholesterol trafficking and Hcy. Methods: ASMase null mice were fed a high-fat ethanol containing diet intragastrically for 4 weeks.