The molecular cloning and expression of a human synaptic vesicle amine transporter that suppresses MPP+ toxicity

Brain Res Mol Brain Res. 1994 Aug;25(1-2):90-6. doi: 10.1016/0169-328x(94)90282-8.

Abstract

A synaptic vesicle amine transporter cDNA, termed hSVAT, has been isolated by the reverse transcription and polymerase chain reaction (PCR) technique from human substantia nigra and subsequent screening of a human substantia nigra library. The hSVAT sequence obtained is highly homologous to the rat SVAT sequence (92% homology) and is essentially identical to the human sequence identified recently by Surratt and colleagues [33]. This labelled hSVAT cDNA detected a single band (approximately 5.0 kb) when used as a probe for Northern analysis of human nigral RNA extract. In situ hybridization studies using hSVAT specific antisense oligonucleotides showed a strong hybridization signal concentrated over the cells of the substantia nigra pars compacta. This cDNA sequence when expressed in chinese hamster ovary (CHO) cells conferred resistance to MPP+ the toxic metabolite of MPTP and cells containing it accumulated dopamine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenylpyridinium / antagonists & inhibitors
  • 1-Methyl-4-phenylpyridinium / toxicity*
  • Amines / metabolism*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Biological Transport / physiology
  • CHO Cells
  • Carrier Proteins / biosynthesis*
  • Cloning, Molecular
  • Cricetinae
  • DNA, Complementary / isolation & purification
  • Genomic Library
  • Humans
  • Molecular Sequence Data
  • Nerve Tissue Proteins / biosynthesis*
  • Substantia Nigra / chemistry
  • Synaptic Vesicles*
  • Transfection

Substances

  • Amines
  • Carrier Proteins
  • DNA, Complementary
  • Nerve Tissue Proteins
  • 1-Methyl-4-phenylpyridinium