Tat-mediated protein transduction of human brain pyridoxal kinase into PC12 cells

Biochimie. 2005 May;87(5):481-7. doi: 10.1016/j.biochi.2004.12.004.

Abstract

Pyridoxal kinase (PK) catalyses the phosphorylation of vitamin B6 to pyridoxal-5'-phosphate (PLP). A human brain PK gene was fused with a gene fragment encoding the HIV-1 Tat protein transduction domain (RKKRRQRRR) in a bacterial expression vector to produce a genetic in-frame Tat-PK fusion protein. The expressed and purified Tat-PK fusion proteins transduced efficiently into PC12 cells in a time- and dose-dependent manner when added exogenously in culture media. Once inside the cells, the transduced Tat-PK proteins showed catalytic activity and are stable for 48 h. The intracellular concentration of PLP, which is known as a biologically active form of vitamin B6, was increased by pre-treatment of Tat-PK to the PC12 cells. Those results suggest that the transduction of Tat-PK fusion protein can be one of the ways to regulate the PLP level and to replenish this enzyme in the various neurological disorders related to vitamin B6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / enzymology*
  • Gene Products, tat / genetics*
  • Genetic Vectors
  • Humans
  • PC12 Cells / metabolism
  • Pyridoxal Kinase / genetics*
  • Rats
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism*
  • Transduction, Genetic*
  • Transfection

Substances

  • Gene Products, tat
  • Recombinant Fusion Proteins
  • Pyridoxal Kinase