Role of Hydroxy acid oxidase 2 (Hao2) in hepatocellular carcinoma
type: CreativeWork
description: Background: Hydroxy acid oxidases are flavin mononucleotide (FMN)-dependent peroxisomal enzymes. Although it is unclear whether 2-hydroxy acid oxidases contribute to a general mechanism of fatty acid α-oxidation, these enzymes are capable of oxidizing a broad range of 2-hydroxy acids, ranging from glycolate to long chain 2-hydroxy fatty acids, such as 2-hydroxypalmitate, to 2-keto acids; this reaction results in hydrogen peroxide (H2O2) formation at the expense of molecular oxygen. Aim: Since no data concerning Hao2, a member of this family, and cancer are available in the literature, we analyzed the expression of this enzyme in mouse, rat and human hepatocellular carcinoma (HCC). Results: Our microarray analysis, performed in the liver of rats subjected to the Resistant Hepatocyte (R-H) model, revealed that Hao2 was among the most down-regulated genes in HCCs developed, 14 months after initiation with a single dose of the hepatocarcinogen Diethylnitrosamine (DENA). Next, we investigated whether Hao2 down-regulation is an early event during liver carcinogenesis; to this aim, we analyzed the expression of Hao2 by qRT-PCR in preneoplastic lesions and HCCs generated 10 weeks, and 14 months after initiation, respectively. Interestingly, qRT-PCR showed down-regulation of Hao2 already in rat early preneoplastic lesions, especially in those positive for the putative progenitor cell marker KRT-19, considered to be the precursor of HCC in this model of hepatocarcinogenesis. Western blot analysis showed Hao2 down-regulation also at protein level. To determine whether this down-regulation is a general phenomenon in liver tumorigenesis or is specific only for rat liver, we analyze the expression of Hao2 in a chemically-induced mouse model of hepatocarcinogenesis, consisting of a single injection of DENA followed by treatment with TCPOBOP (1,4-bis[2-(3,5-dichloropyridyloxy)] benzene), a ligand of the nuclear receptor CAR (Constitutive androstane receptor), that causes massive he…
abstract: Background: Hydroxy acid oxidases are flavin mononucleotide (FMN)-dependent peroxisomal enzymes. Although it is unclear whether 2-hydroxy acid oxidases contribute to a general mechanism of fatty acid α-oxidation, these enzymes are capable of oxidizing a broad range of 2-hydroxy acids, ranging from glycolate to long chain 2-hydroxy fatty acids, such as 2-hydroxypalmitate, to 2-keto acids; this reaction results in hydrogen peroxide (H2O2) formation at the expense of molecular oxygen. Aim: Since no data concerning Hao2, a member of this family, and cancer are available in the literature, we analyzed the expression of this enzyme in mouse, rat and human hepatocellular carcinoma (HCC). Results: Our microarray analysis, performed in the liver of rats subjected to the Resistant Hepatocyte (R-H) model, revealed that Hao2 was among the most down-regulated genes in HCCs developed, 14 months after initiation with a single dose of the hepatocarcinogen Diethylnitrosamine (DENA). Next, we investigated whether Hao2 down-regulation is an early event during liver carcinogenesis; to this aim, we analyzed the expression of Hao2 by qRT-PCR in preneoplastic lesions and HCCs generated 10 weeks, and 14 months after initiation, respectively. Interestingly, qRT-PCR showed down-regulation of Hao2 already in rat early preneoplastic lesions, especially in those positive for the putative progenitor cell marker KRT-19, considered to be the precursor of HCC in this model of hepatocarcinogenesis. Western blot analysis showed Hao2 down-regulation also at protein level. To determine whether this down-regulation is a general phenomenon in liver tumorigenesis or is specific only for rat liver, we analyze the expression of Hao2 in a chemically-induced mouse model of hepatocarcinogenesis, consisting of a single injection of DENA followed by treatment with TCPOBOP (1,4-bis[2-(3,5-dichloropyridyloxy)] benzene), a ligand of the nuclear receptor CAR (Constitutive androstane receptor), that causes massive he…
author: MATTU, SANDRA
language: eng
keywords: Hydroxy acid oxidase 2 (Hao2), carcinoma epatocellulare, fegato, hepatocellular carcinoma, idrossiacidoossidasi-2 (Hao2), liver, Settore MED/04 - Patologia Generale
date published: 2015-05-06
date modified: 2026-07-24T01:30:01Z
provider: Università di Cagliari
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Cagliari

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property ID: Handle
value: http://hdl.handle.net/11584/266367