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Covalent peroxisome proliferator-activated receptor gamma adduction by nitro-fatty acids: selective ligand activity and anti-diabetic signaling actions

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Covalent peroxisome proliferator-activated receptor gamma adduction by nitro-fatty acids: selective ligand activity and anti-diabetic signaling actions. / Schopfer, Francisco J; Cole, Marsha P; Groeger, Alison L; Chen, Chen-Shan; Khoo, Nicholas K H; Woodcock, Steven R; Golin-Bisello, Franca; Motanya, U Nkiru; Li, Yong; Zhang, Jifeng; Garcia-Barrio, Minerva T; Rudolph, Tanja K; Rudolph, Volker; Bonacci, Gustavo; Baker, Paul R S; Xu, H Eric; Batthyany, Carlos I; Chen, Y Eugene; Hallis, Tina M; Freeman, Bruce A.

In: J BIOL CHEM, Vol. 285, No. 16, 16.04.2010, p. 12321-12333.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Schopfer, FJ, Cole, MP, Groeger, AL, Chen, C-S, Khoo, NKH, Woodcock, SR, Golin-Bisello, F, Motanya, UN, Li, Y, Zhang, J, Garcia-Barrio, MT, Rudolph, TK, Rudolph, V, Bonacci, G, Baker, PRS, Xu, HE, Batthyany, CI, Chen, YE, Hallis, TM & Freeman, BA 2010, 'Covalent peroxisome proliferator-activated receptor gamma adduction by nitro-fatty acids: selective ligand activity and anti-diabetic signaling actions', J BIOL CHEM, vol. 285, no. 16, pp. 12321-12333. https://doi.org/10.1074/jbc.M109.091512

APA

Schopfer, F. J., Cole, M. P., Groeger, A. L., Chen, C-S., Khoo, N. K. H., Woodcock, S. R., Golin-Bisello, F., Motanya, U. N., Li, Y., Zhang, J., Garcia-Barrio, M. T., Rudolph, T. K., Rudolph, V., Bonacci, G., Baker, P. R. S., Xu, H. E., Batthyany, C. I., Chen, Y. E., Hallis, T. M., & Freeman, B. A. (2010). Covalent peroxisome proliferator-activated receptor gamma adduction by nitro-fatty acids: selective ligand activity and anti-diabetic signaling actions. J BIOL CHEM, 285(16), 12321-12333. https://doi.org/10.1074/jbc.M109.091512

Vancouver

Schopfer FJ, Cole MP, Groeger AL, Chen C-S, Khoo NKH, Woodcock SR et al. Covalent peroxisome proliferator-activated receptor gamma adduction by nitro-fatty acids: selective ligand activity and anti-diabetic signaling actions. J BIOL CHEM. 2010 Apr 16;285(16):12321-12333. https://doi.org/10.1074/jbc.M109.091512

Bibtex

@article{6e6da244afe446a7a45d0faf7d376160,
title = "Covalent peroxisome proliferator-activated receptor gamma adduction by nitro-fatty acids: selective ligand activity and anti-diabetic signaling actions",
abstract = "The peroxisome proliferator-activated receptor-gamma (PPARgamma) binds diverse ligands to transcriptionally regulate metabolism and inflammation. Activators of PPARgamma include lipids and anti-hyperglycemic drugs such as thiazolidinediones (TZDs). Recently, TZDs have raised concern after being linked with increased risk of peripheral edema, weight gain, and adverse cardiovascular events. Most reported endogenous PPARgamma ligands are intermediates of lipid metabolism and oxidation that bind PPARgamma with very low affinity. In contrast, nitro derivatives of unsaturated fatty acids (NO(2)-FA) are endogenous products of nitric oxide ((*)NO) and nitrite (NO(2)(-))-mediated redox reactions that activate PPARgamma at nanomolar concentrations. We report that NO(2)-FA act as partial agonists of PPARgamma and covalently bind PPARgamma at Cys-285 via Michael addition. NO(2)-FA show selective PPARgamma modulator characteristics by inducing coregulator protein interactions, PPARgamma-dependent expression of key target genes, and lipid accumulation is distinctively different from responses induced by the TZD rosiglitazone. Administration of this class of signaling mediators to ob/ob mice revealed that NO(2)-FA lower insulin and glucose levels without inducing adverse side effects such as the increased weight gain induced by TZDs.",
keywords = "3T3-L1 Cells, Amino Acid Sequence, Amino Acid Substitution, Animals, Base Sequence, Blood Glucose/metabolism, Cell Line, DNA Primers/metabolism, Diabetes Mellitus/drug therapy, Fatty Acids, Unsaturated/chemistry, Humans, Hypoglycemic Agents/chemistry, In Vitro Techniques, Insulin/blood, Ligands, Lipid Metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Obese, Molecular Sequence Data, Mutagenesis, Site-Directed, Nitro Compounds/chemistry, Oleic Acid/chemistry, PPAR gamma/agonists, Protein Binding, Protein Processing, Post-Translational, Protein Structure, Tertiary, Recombinant Proteins/chemistry, Rosiglitazone, Signal Transduction, Tandem Mass Spectrometry, Thiazolidinediones/pharmacology",
author = "Schopfer, {Francisco J} and Cole, {Marsha P} and Groeger, {Alison L} and Chen-Shan Chen and Khoo, {Nicholas K H} and Woodcock, {Steven R} and Franca Golin-Bisello and Motanya, {U Nkiru} and Yong Li and Jifeng Zhang and Garcia-Barrio, {Minerva T} and Rudolph, {Tanja K} and Volker Rudolph and Gustavo Bonacci and Baker, {Paul R S} and Xu, {H Eric} and Batthyany, {Carlos I} and Chen, {Y Eugene} and Hallis, {Tina M} and Freeman, {Bruce A}",
year = "2010",
month = apr,
day = "16",
doi = "10.1074/jbc.M109.091512",
language = "English",
volume = "285",
pages = "12321--12333",
journal = "J BIOL CHEM",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "16",

}

RIS

TY - JOUR

T1 - Covalent peroxisome proliferator-activated receptor gamma adduction by nitro-fatty acids: selective ligand activity and anti-diabetic signaling actions

AU - Schopfer, Francisco J

AU - Cole, Marsha P

AU - Groeger, Alison L

AU - Chen, Chen-Shan

AU - Khoo, Nicholas K H

AU - Woodcock, Steven R

AU - Golin-Bisello, Franca

AU - Motanya, U Nkiru

AU - Li, Yong

AU - Zhang, Jifeng

AU - Garcia-Barrio, Minerva T

AU - Rudolph, Tanja K

AU - Rudolph, Volker

AU - Bonacci, Gustavo

AU - Baker, Paul R S

AU - Xu, H Eric

AU - Batthyany, Carlos I

AU - Chen, Y Eugene

AU - Hallis, Tina M

AU - Freeman, Bruce A

PY - 2010/4/16

Y1 - 2010/4/16

N2 - The peroxisome proliferator-activated receptor-gamma (PPARgamma) binds diverse ligands to transcriptionally regulate metabolism and inflammation. Activators of PPARgamma include lipids and anti-hyperglycemic drugs such as thiazolidinediones (TZDs). Recently, TZDs have raised concern after being linked with increased risk of peripheral edema, weight gain, and adverse cardiovascular events. Most reported endogenous PPARgamma ligands are intermediates of lipid metabolism and oxidation that bind PPARgamma with very low affinity. In contrast, nitro derivatives of unsaturated fatty acids (NO(2)-FA) are endogenous products of nitric oxide ((*)NO) and nitrite (NO(2)(-))-mediated redox reactions that activate PPARgamma at nanomolar concentrations. We report that NO(2)-FA act as partial agonists of PPARgamma and covalently bind PPARgamma at Cys-285 via Michael addition. NO(2)-FA show selective PPARgamma modulator characteristics by inducing coregulator protein interactions, PPARgamma-dependent expression of key target genes, and lipid accumulation is distinctively different from responses induced by the TZD rosiglitazone. Administration of this class of signaling mediators to ob/ob mice revealed that NO(2)-FA lower insulin and glucose levels without inducing adverse side effects such as the increased weight gain induced by TZDs.

AB - The peroxisome proliferator-activated receptor-gamma (PPARgamma) binds diverse ligands to transcriptionally regulate metabolism and inflammation. Activators of PPARgamma include lipids and anti-hyperglycemic drugs such as thiazolidinediones (TZDs). Recently, TZDs have raised concern after being linked with increased risk of peripheral edema, weight gain, and adverse cardiovascular events. Most reported endogenous PPARgamma ligands are intermediates of lipid metabolism and oxidation that bind PPARgamma with very low affinity. In contrast, nitro derivatives of unsaturated fatty acids (NO(2)-FA) are endogenous products of nitric oxide ((*)NO) and nitrite (NO(2)(-))-mediated redox reactions that activate PPARgamma at nanomolar concentrations. We report that NO(2)-FA act as partial agonists of PPARgamma and covalently bind PPARgamma at Cys-285 via Michael addition. NO(2)-FA show selective PPARgamma modulator characteristics by inducing coregulator protein interactions, PPARgamma-dependent expression of key target genes, and lipid accumulation is distinctively different from responses induced by the TZD rosiglitazone. Administration of this class of signaling mediators to ob/ob mice revealed that NO(2)-FA lower insulin and glucose levels without inducing adverse side effects such as the increased weight gain induced by TZDs.

KW - 3T3-L1 Cells

KW - Amino Acid Sequence

KW - Amino Acid Substitution

KW - Animals

KW - Base Sequence

KW - Blood Glucose/metabolism

KW - Cell Line

KW - DNA Primers/metabolism

KW - Diabetes Mellitus/drug therapy

KW - Fatty Acids, Unsaturated/chemistry

KW - Humans

KW - Hypoglycemic Agents/chemistry

KW - In Vitro Techniques

KW - Insulin/blood

KW - Ligands

KW - Lipid Metabolism

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Obese

KW - Molecular Sequence Data

KW - Mutagenesis, Site-Directed

KW - Nitro Compounds/chemistry

KW - Oleic Acid/chemistry

KW - PPAR gamma/agonists

KW - Protein Binding

KW - Protein Processing, Post-Translational

KW - Protein Structure, Tertiary

KW - Recombinant Proteins/chemistry

KW - Rosiglitazone

KW - Signal Transduction

KW - Tandem Mass Spectrometry

KW - Thiazolidinediones/pharmacology

U2 - 10.1074/jbc.M109.091512

DO - 10.1074/jbc.M109.091512

M3 - SCORING: Journal article

C2 - 20097754

VL - 285

SP - 12321

EP - 12333

JO - J BIOL CHEM

JF - J BIOL CHEM

SN - 0021-9258

IS - 16

ER -