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Melanocortin receptors in rat liver cells: change of gene expression and intracellular localization during acute-phase response.

ABSTRACT: MCRs are known to be expressed predominantly in the brain where they mediate metabolic and anti-inflammatory functions. Leptin plays an important role in appetite and energy regulation via signaling through melanocortin receptors (MCRs) in the brain. As serum levels of MCR ligands are elevated in a clinical situation [acute-phase response (APR)] to tissue damage, where the liver is responsible for the metabolic changes, we studied hepatic gene expression of MCRs in a model of muscle tissue damage induced by turpentine oil (TO) injection in rats. A significant increase in gene expression of all five MCRs (MC4R was the highest) in liver at the RNA and protein level was detected after TO injection. A similar pattern of increase was also found in the brain. Immunohistology showed MC4R in the cytoplasm, but also in the nucleus of parenchymal and non-parenchymal liver cells, whereas MC3R-positivity was mainly cytoplasmic. A time-dependent migration of MC4R protein from the cytoplasm into the nucleus was observed during APR, in parallel with an increase in ?-MSH and leptin serum levels. An increase of MC4R was detected at the protein level in wild-type mice, while such an increase was not observed in IL-6ko mice during APR. Moreover, treatment of isolated liver cells with melanocortin agonists (?-MSH and THIQ) inhibited the endotoxin-induced upregulation of the acute-phase cytokine (IL-6, IL1? and TNF-?) gene expression in Kupffer cells and of chemokine gene expression in hepatocytes. MCRs are expressed not only in the brain, but also in liver cells and their gene expression in liver and brain tissue is upregulated during APR. Due to the presence of specific ligands in the serum, they may mediate metabolic changes and exert a protective effect on liver cells.

SUBMITTER: Malik IA

PROVIDER: S-EPMC3312751 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Melanocortin receptors in rat liver cells: change of gene expression and intracellular localization during acute-phase response.

Malik Ihtzaz Ahmed IA Triebel Jakob J Posselt Jessica J Khan Sajjad S Ramadori Pierluigi P Raddatz Dirk D Ramadori Giuliano G

Histochemistry and cell biology 20111220 3

MCRs are known to be expressed predominantly in the brain where they mediate metabolic and anti-inflammatory functions. Leptin plays an important role in appetite and energy regulation via signaling through melanocortin receptors (MCRs) in the brain. As serum levels of MCR ligands are elevated in a clinical situation [acute-phase response (APR)] to tissue damage, where the liver is responsible for the metabolic changes, we studied hepatic gene expression of MCRs in a model of muscle tissue damag ...[more]

PMID: 22183812

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Project description:BACKGROUND:ATP-sensitive K+ (KATP) channels were originally found in cardiac myocytes by Noma in 1983. KATP channels were formed by potassium ion-passing pore-forming subunits (Kir6.1, Kir6.2) and regulatory subunits SUR1, SU2A and SUR2B. A number of cells and tissues have been revealed to contain these channels including hepatocytes, but detailed localization of these subunits in different types of liver cells was still uncertain. AIM:To investigate the expression of KATP channel subunits in rat liver and their localization in different cells of the liver. METHODS:Rabbit anti-rat SUR1 peptide antibody was raised and purified by antigen immunoaffinity column chromatography. Four of Sprague-Dawley rats were used for liver protein extraction for immunoblot analysis, seven of them were used for immunohistochemistry both for the ABC method and immunofluorescence staining. Four of Wistar rats were used for the isolation of hepatic stellate cells (HSCs) and Kupffer cells for both primary culture and immunocytochemistry. RESULTS:Immunoblot analysis showed that the five kinds of KATP channel subunits, i.e. Kir6.1, Kir6.2, SUR1, SUR2A, and SUR2B, were detected in liver. Immunohistochemical staining showed that Kir6.1 and Kir6.2 were weakly to moderately expressed in parenchymal cells and sinusoidal lining cells, while SUR1, SUR2A, and SUR2B were mainly localized to sinusoidal lining cells, such as HSCs, Kupffer cells, and sinusoidal endothelial cells. Immunoreactivity for SUR2A and SUR2B was expressed in the hepatocyte membrane. Double immunofluorescence staining further showed that the pore-forming subunits Kir6.1 and/or Kir6.2 colocalized with GFAP in rat liver sections and primary cultured HSCs. These KATP channel subunits also colocalized with CD68 in liver sections and primary cultured Kupffer cells. The SUR subunits colocalized with GFAP in liver sections and colocalized with CD68 both in liver sections and primary cultured Kupffer cells. In addition, five KATP channel subunits colocalized with SE-1 in sinusoidal endothelial cells. CONCLUSION:Observations from the present study indicated that KATP channel subunits expressed in rat liver and the diversity of KATP channel subunit composition might form different types of KATP channels. This is applicable to hepatocytes, HSCs, various types of Kupffer cells and sinusoidal endothelial cells.

Dataset Information

Melanocortin receptors in rat liver cells: change of gene expression and intracellular localization during acute-phase response.

Publications

Melanocortin receptors in rat liver cells: change of gene expression and intracellular localization during acute-phase response.

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