Kinetic studies of FR-1, a growth factor-inducible aldo-keto reductase

Sanjay Srivastava, Theresa M. Harter, Animesh Chandra, Aruni Bhatnagar, Satish K. Srivastava, J. Mark Petrash

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Murine fibroblasts cultured in the presence of fibroblast growth factor- 1 express relatively high levels of FR-1, a ~36 kDa protein related to the aldo-keto reductase superfamily [Donohue, P. J., Alberts, G. F., Hampton, B. S., Winkles, J. A. (1994) J. BioI. Chem. 269, 8604-8609]. While the crystal structure of FR-I shows striking homology with human aldose reductase [Wilson, D. K., Nakano, T., Petrash, J. M., Quiocho, F. A. (1995) Biochemistry, 34, 14323-14330], an enzyme linked to the pathogenesis of diabetic complications, the physiological role of FR-1 is not known. We show that FR-1 is capable of reducing a broad range of aromatic and aliphatic aldehydes, including the abundant and highly reactive lipid-derived aldehyde 4-hydroxy-2-nonenal (HNE; K(m) ≃ 9 μM). However, in the absence of coenzyme, HNE caused a time-dependent inactivation of FR-1. Results from electrospray ionization-mass spectrometry and Edman-degradation of peptides derived from HNE-modified FR-1 were consistent with formation of a Michael adduct at Cys298. This was confirmed with a C298S mutant, which was resistant to HNE-induced inactivation. Since steady-state K(m) values determined with alkanals, α,β-unsaturated alkenals, alkadienals, and 4-hydroxyalkenals fall within their physiological concentrations, lipid-derived aldehydes appear to be potential in vivo substrates for FR-1.

Original languageEnglish (US)
Pages (from-to)12909-12917
Number of pages9
JournalBiochemistry
Volume37
Issue number37
DOIs
StatePublished - Sep 15 1998

ASJC Scopus subject areas

  • Biochemistry

Fingerprint Dive into the research topics of 'Kinetic studies of FR-1, a growth factor-inducible aldo-keto reductase'. Together they form a unique fingerprint.

  • Cite this

    Srivastava, S., Harter, T. M., Chandra, A., Bhatnagar, A., Srivastava, S. K., & Petrash, J. M. (1998). Kinetic studies of FR-1, a growth factor-inducible aldo-keto reductase. Biochemistry, 37(37), 12909-12917. https://doi.org/10.1021/bi9804333