Expression of organic osmolyte transporters in cultured rat astrocytes and rat and human cerebral cortex

Arch Biochem Biophys. 2014 Oct 15:560:59-72. doi: 10.1016/j.abb.2014.06.024. Epub 2014 Jul 5.

Abstract

This study characterizes the expression of the osmolyte transporters betaine/γ-amino-n-butyric acid (GABA) transporter (BGT-1), the taurine transporter (TauT) and the sodium-dependent myo-inositol transporter (SMIT) in various rat brain cells in culture and in rat and human cerebral cortex in situ. Osmolyte transporter expression greatly differed between cultured brain cells with highest mRNA expression levels for SMIT in astrocytes and TauT in neurons. BGT-1 mRNA and protein were expressed in microglia but not in astrocytes and neurons. In rat and human cerebral cortex, SMIT was expressed in astrocytes and TauT was found in neurons. Osmolyte transporter expression was subject to regulation by factors relevant for hepatic encephalopathy (HE). Hypoosmolarity, NH4Cl (0.5-5 mmol/l), diazepam (10 μmol/l) and TNFα (10 ng/ml) time-dependently decreased mRNA expression of SMIT and/or TauT in cultured astrocytes. NH4Cl-induced SMIT/TauT mRNA expression changes were sensitive to inhibitors of glutamine synthetase and NADPH oxidase. In rat cerebral cortex, SMIT mRNA expression decreased after portal vein ligation or ammonium acetate injection probably due to astrocyte swelling in these HE animal models. It is concluded that osmolyte transporters are heterogeneously expressed in brain and are subject to regulation by HE-relevant factors.

Keywords: Ammonia; Astrocytes; Hepatic encephalopathy; Osmolyte transporter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / toxicity
  • Animals
  • Astrocytes / cytology
  • Astrocytes / drug effects
  • Astrocytes / metabolism*
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • Gene Expression Regulation* / drug effects
  • Humans
  • Ligation
  • Male
  • Membrane Transport Proteins / genetics*
  • Portal Vein / surgery
  • Rats

Substances

  • Acetates
  • Membrane Transport Proteins
  • ammonium acetate