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

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

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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

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Aldehydes
Intercellular Signaling Peptides and Proteins
Kinetics
Lipids
Fibroblast Growth Factor 1
Aldehyde Reductase
Electrospray ionization
Biochemistry
Electrospray Ionization Mass Spectrometry
Coenzymes
Diabetes Complications
Fibroblasts
Mass spectrometry
Crystal structure
Degradation
Peptides
Substrates
Enzymes
carbonyl reductase (NADPH)
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Srivastava, S., Harter, T. M., Chandra, A., Bhatnagar, A., Srivastava, S., & 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

Kinetic studies of FR-1, a growth factor-inducible aldo-keto reductase. / Srivastava, Sanjay; Harter, Theresa M.; Chandra, Animesh; Bhatnagar, Aruni; Srivastava, Satish; Petrash, J. Mark.

In: Biochemistry, Vol. 37, No. 37, 15.09.1998, p. 12909-12917.

Research output: Contribution to journalArticle

Srivastava, S, Harter, TM, Chandra, A, Bhatnagar, A, Srivastava, S & Petrash, JM 1998, 'Kinetic studies of FR-1, a growth factor-inducible aldo-keto reductase', Biochemistry, vol. 37, no. 37, pp. 12909-12917. https://doi.org/10.1021/bi9804333
Srivastava S, Harter TM, Chandra A, Bhatnagar A, Srivastava S, Petrash JM. Kinetic studies of FR-1, a growth factor-inducible aldo-keto reductase. Biochemistry. 1998 Sep 15;37(37):12909-12917. https://doi.org/10.1021/bi9804333
Srivastava, Sanjay ; Harter, Theresa M. ; Chandra, Animesh ; Bhatnagar, Aruni ; Srivastava, Satish ; Petrash, J. Mark. / Kinetic studies of FR-1, a growth factor-inducible aldo-keto reductase. In: Biochemistry. 1998 ; Vol. 37, No. 37. pp. 12909-12917.
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