Reduction of derived aldehydes by a fibro blast growth factor-induced enyzme, FR-I

S. Srivastava, A. Chandra, A. Bhatnagar, J. M. Petrash, Satish Srivastava

Research output: Contribution to journalArticle

Abstract

Free radicals-catalyzed peroxidation of polyunsaturated fatty acids yields alkanals, alkenals, 4-hydroxyalkenals and alkadienals, which can act as toxic second messengers and lead to spatial and temporal extension of the injurious potential of the initial free radical events. We show that murine fibroblast growth factor-regulated enzyme (FR-I) catalyses the reduction the lipid derived aldehydes. K", aldehydes decreased as a function of chain length. The aldehydes with nine carbons viz. nonanal, nonenal, 4-hydroxynonenal (HNE) and nonadienal have a K" of 8-10 uM as compared to K m j,rolmi| and K(tm) cioionaiddiydc. 3-5 mM. The catalytic efficiency of C-9 compounds increased by more than 500 fold as compared to C-3 and C-4 compounds. Incubation of the apoenzyme with 'H-HNE led to an irrversible loss of activity. Sequence analysis of the radiolabeled peptides revealed the modification of Cys-299. The Cys-299 mutant was insensitive to HNE-induced modification of the enzyme and Km of 4-hydroxyalkenals increased by 5 to 10 fold for the mutant enzyme. These studies indicate that FR-I which has - 70% homology with mammalian aldose reductase and comparable active site, could play a pivotal role in the detoxification of lipid derived aldehydes.

Original languageEnglish (US)
JournalFASEB Journal
Volume11
Issue number9
StatePublished - 1997
Externally publishedYes

Fingerprint

fibroblast growth factors
Aldehydes
aldehydes
Intercellular Signaling Peptides and Proteins
Free Radicals
Enzymes
enzymes
aldehyde reductase
Apoenzymes
Lipids
Aldehyde Reductase
mutants
Detoxification
apoproteins
Fibroblast Growth Factors
Poisons
second messengers
peroxidation
Protein Sequence Analysis
Second Messenger Systems

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Srivastava, S., Chandra, A., Bhatnagar, A., Petrash, J. M., & Srivastava, S. (1997). Reduction of derived aldehydes by a fibro blast growth factor-induced enyzme, FR-I. FASEB Journal, 11(9).

Reduction of derived aldehydes by a fibro blast growth factor-induced enyzme, FR-I. / Srivastava, S.; Chandra, A.; Bhatnagar, A.; Petrash, J. M.; Srivastava, Satish.

In: FASEB Journal, Vol. 11, No. 9, 1997.

Research output: Contribution to journalArticle

Srivastava, S, Chandra, A, Bhatnagar, A, Petrash, JM & Srivastava, S 1997, 'Reduction of derived aldehydes by a fibro blast growth factor-induced enyzme, FR-I', FASEB Journal, vol. 11, no. 9.
Srivastava S, Chandra A, Bhatnagar A, Petrash JM, Srivastava S. Reduction of derived aldehydes by a fibro blast growth factor-induced enyzme, FR-I. FASEB Journal. 1997;11(9).
Srivastava, S. ; Chandra, A. ; Bhatnagar, A. ; Petrash, J. M. ; Srivastava, Satish. / Reduction of derived aldehydes by a fibro blast growth factor-induced enyzme, FR-I. In: FASEB Journal. 1997 ; Vol. 11, No. 9.
@article{28d5aaa04e2545f0954cd7a9126ce4e2,
title = "Reduction of derived aldehydes by a fibro blast growth factor-induced enyzme, FR-I",
abstract = "Free radicals-catalyzed peroxidation of polyunsaturated fatty acids yields alkanals, alkenals, 4-hydroxyalkenals and alkadienals, which can act as toxic second messengers and lead to spatial and temporal extension of the injurious potential of the initial free radical events. We show that murine fibroblast growth factor-regulated enzyme (FR-I) catalyses the reduction the lipid derived aldehydes. K{"}, aldehydes decreased as a function of chain length. The aldehydes with nine carbons viz. nonanal, nonenal, 4-hydroxynonenal (HNE) and nonadienal have a K{"} of 8-10 uM as compared to K m j,rolmi| and K(tm) cioionaiddiydc. 3-5 mM. The catalytic efficiency of C-9 compounds increased by more than 500 fold as compared to C-3 and C-4 compounds. Incubation of the apoenzyme with 'H-HNE led to an irrversible loss of activity. Sequence analysis of the radiolabeled peptides revealed the modification of Cys-299. The Cys-299 mutant was insensitive to HNE-induced modification of the enzyme and Km of 4-hydroxyalkenals increased by 5 to 10 fold for the mutant enzyme. These studies indicate that FR-I which has - 70{\%} homology with mammalian aldose reductase and comparable active site, could play a pivotal role in the detoxification of lipid derived aldehydes.",
author = "S. Srivastava and A. Chandra and A. Bhatnagar and Petrash, {J. M.} and Satish Srivastava",
year = "1997",
language = "English (US)",
volume = "11",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "9",

}

TY - JOUR

T1 - Reduction of derived aldehydes by a fibro blast growth factor-induced enyzme, FR-I

AU - Srivastava, S.

AU - Chandra, A.

AU - Bhatnagar, A.

AU - Petrash, J. M.

AU - Srivastava, Satish

PY - 1997

Y1 - 1997

N2 - Free radicals-catalyzed peroxidation of polyunsaturated fatty acids yields alkanals, alkenals, 4-hydroxyalkenals and alkadienals, which can act as toxic second messengers and lead to spatial and temporal extension of the injurious potential of the initial free radical events. We show that murine fibroblast growth factor-regulated enzyme (FR-I) catalyses the reduction the lipid derived aldehydes. K", aldehydes decreased as a function of chain length. The aldehydes with nine carbons viz. nonanal, nonenal, 4-hydroxynonenal (HNE) and nonadienal have a K" of 8-10 uM as compared to K m j,rolmi| and K(tm) cioionaiddiydc. 3-5 mM. The catalytic efficiency of C-9 compounds increased by more than 500 fold as compared to C-3 and C-4 compounds. Incubation of the apoenzyme with 'H-HNE led to an irrversible loss of activity. Sequence analysis of the radiolabeled peptides revealed the modification of Cys-299. The Cys-299 mutant was insensitive to HNE-induced modification of the enzyme and Km of 4-hydroxyalkenals increased by 5 to 10 fold for the mutant enzyme. These studies indicate that FR-I which has - 70% homology with mammalian aldose reductase and comparable active site, could play a pivotal role in the detoxification of lipid derived aldehydes.

AB - Free radicals-catalyzed peroxidation of polyunsaturated fatty acids yields alkanals, alkenals, 4-hydroxyalkenals and alkadienals, which can act as toxic second messengers and lead to spatial and temporal extension of the injurious potential of the initial free radical events. We show that murine fibroblast growth factor-regulated enzyme (FR-I) catalyses the reduction the lipid derived aldehydes. K", aldehydes decreased as a function of chain length. The aldehydes with nine carbons viz. nonanal, nonenal, 4-hydroxynonenal (HNE) and nonadienal have a K" of 8-10 uM as compared to K m j,rolmi| and K(tm) cioionaiddiydc. 3-5 mM. The catalytic efficiency of C-9 compounds increased by more than 500 fold as compared to C-3 and C-4 compounds. Incubation of the apoenzyme with 'H-HNE led to an irrversible loss of activity. Sequence analysis of the radiolabeled peptides revealed the modification of Cys-299. The Cys-299 mutant was insensitive to HNE-induced modification of the enzyme and Km of 4-hydroxyalkenals increased by 5 to 10 fold for the mutant enzyme. These studies indicate that FR-I which has - 70% homology with mammalian aldose reductase and comparable active site, could play a pivotal role in the detoxification of lipid derived aldehydes.

UR - http://www.scopus.com/inward/record.url?scp=33750195879&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750195879&partnerID=8YFLogxK

M3 - Article

VL - 11

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 9

ER -