Proteomic analysis of nicotine-associated protein expression in the striatum of repeated nicotine-treated rats

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Abstract

Through the proteomic analysis using 2-dimensional electrophoresis, the nicotine addiction-associated proteins were extensively screened in the striatum of rat brains. The nicotine addiction was developed by repeated nicotine injection (0.4 mg/kg s.c.), twice daily for 7 days, followed by one challenge injection after a 3 day withdrawal period, and then confirmed by observing a 2.3-fold increase in locomoter activity. The 3 up- and 4 down-regulated proteins were selected and identified to be zinc-finger binding protein-89 (ZBP-89), 2′3′-cyclic nucleotide 3′-phosphodiesterase 1, deoxyribonuclease 1-like 3 (DNase1l3), tandem pore domain halothane inhibited K+ channel (THIK-2), brain-specific hyaluronan-binding protein (BRAL-1), death effector domain-containing DNA binding protein (DEDD), and brain-derived neurotrophic factor (BDNF) by mass spectrophotometric fingerprinting. Among them, the expression patterns of ZEB-89, DNase1l3, THIK-2, DEDD, and BDNF mRNAs were found to be coincident with those of cognate proteins, by using RT-PCR analysis. These proteins could be suggested as drug targets to develop a new therapy for nicotine-associated diseases, as well as the clues to understand the mechanism of nicotine.

Section snippets

Materials and methods

Animals and nicotine treatment. Male Sprague–Dawley rats weighing 250–280 g at the start of experiments were used throughout. Prior to the experimental manipulation, the animals were given a period of 1 week to adjust to the new environment. Animals were cared for and handled in accordance with the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals. Animals were divided randomly into nicotine-treated (NIC, n = 10) and control (CONT, n = 10) groups. For nicotine

Results and discussion

Tobacco smoking still remains a major health problem worldwide. Nicotine is a principal component of tobacco, eliciting addictive behavior in human [1], [5], [6]. Intermittent nicotine administration brings about the behavioral sensitization, which is defined as an increased behavioral and/or neurochemical response [8]. Locomotor activation and reinforcement may be relevant to the stimulatory effects of nicotine on the mesolimbic dopaminergic system [18]. The striatum and nucleus accumbens are

Acknowledgments

The authors thank Prof. Kang-Duk Choi at Hankyong National University for the technical support and the helpful discussion. This study was supported by the Brain Korea 21 Project from the Ministry of Education, Republic of Korea.

References (48)

  • A. Moller et al.

    Two-dimensional gel electrophoresis: a powerful method to elucidate cellular responses to toxic compounds

    Toxicology

    (2001)
  • T.S. Rao et al.

    Pharmacological characterization of SIB-1663, a conformationally rigid analog of nicotine

    Brain Res.

    (2004)
  • Y. Jiang et al.

    Up-regulation of murine double minute clone 2 (MDM2) gene expression in rat brain after morphine, heroin, and cocaine administrations

    Neurosci. Lett.

    (2003)
  • H. Mai et al.

    A functional role for nicotine in Bcl2 phosphorylation and suppression of apoptosis

    J. Biol. Chem.

    (2003)
  • S.S. Scherer et al.

    Differential regulation of the 2′,3′-cyclic nucleotide 3′-phosphodiesterase gene during oligodendrocyte development

    Neuron

    (1994)
  • A. Wilber et al.

    Deoxyribonuclease I-like III is an inducible macrophage barrier to liposomal transfection

    Mol. Ther.

    (2002)
  • S. Rajan et al.

    THIK-1 and THIK-2, a novel subfamily of tandem pore domain K+ channels

    J. Biol. Chem.

    (2001)
  • S. Hirakawa et al.

    The brain link protein-1 (BRAL1): cDNA cloning, genomic structure, and characterization as a novel link protein expressed in adult brain

    Biochem. Biophys. Res. Commun.

    (2000)
  • T. Oohashi et al.

    Bral1, a brain-specific link protein, colocalizing with the versican V2 isoform at the nodes of Ranvier in developing and adult mouse central nervous systems

    Mol. Cell. Neurosci.

    (2002)
  • M.T. Berhow et al.

    Influence of neurotrophic factors on morphine- and cocaine-induced biochemical changes in the mesolimbic dopamine system

    Neuroscience

    (1995)
  • P.J. Kenny et al.

    Acute nicotine decreases, and chronic nicotine increases the expression of brain-derived neurotrophic factor mRNA in rat hippocampus

    Brain Res. Mol. Brain Res.

    (2000)
  • G.E. Meredith et al.

    Brain-derived neurotrophic factor expression is increased in the rat amygdala, piriform cortex and hypothalamus following repeated amphetamine administration

    Brain Res.

    (2002)
  • J.L. Galzi et al.

    Neuronal nicotinic receptors: molecular organization and regulations

    Neuropharmacology

    (1995)
  • WHO, The World Health Report, ed., World Health Organization Publications,...
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