Molecular mechanisms in signaling of nitrated fatty acids

Work team

Research projects

Our objective is to contribute to the understanding of the biological function of nitro-fatty acid and electrophilic molecules in different inflammatory models. These bioactive molecules are highly reactive with nucleophiles inducing posttraslational modification (PTM) in important regulatory proteins. This modification is responsible for changing the biological function of target protein such as catalytic activity, traffic and cellular localization. Nitrated lipids formation increase in inflammatory environments of atherosclerosis and immune disorders.

Therefore, our lab is currently exploring how nitrolipids modulate scavenger receptors (CD36, SR-A and LRP-1) in monocytes-macrophages and their relationship with atherosclerosis. The expression of scavenger receptor in monocytes-macrophages is clinically relevant because of the direct association with the grade of atherosclerotic lesion. CD36 and SR-A mediate the uptake of abnormal lipoproteins (oxidized and acetylated-LDL) which induce the transformation of macrophage to foam cell in the atheroma plaque. Thus, our overall mission is to identify novel mediator, pathways and critical target for these molecules as possible anti-inflammatory candidate to regulate the development of pathological process such as diabetes and cardiovascular disease. 

Publications

Kelley EE, Baust J, Sonia G, Cantu-Medellin N, Bonacci G, Golin-Bisello F, Devlin JE, Croix CM, Watkins SC, Gladwin MT, Champion HC, Freeman BA, Khoo NKH.

Fatty acid nitroalkenes ameliorate glucose intolerance and pulmonary hypertension in high fat diet-induced obesity. Cardiovasc Res. 2014 Mar 1;101(3):352-63.

Woodcock Sr, Salvatore SR, Bonacci G, Schopfer FJ, Freeman BA.

Biomimetic Nitration of Conjugated Linoleic Acid: Formation and Characterization of Naturally Occurring Conjugated Nitrodienes. J. Org. Chem. 2014 Jan 3;79(1):25-33.

Vitturi DA, Chen CS, Woodcock SR, Salvatore SR, Bonacci G, Koenitzer JR, Stewart NA, Wakabayashi N, Kensler TW, Freeman BA, Schopfer FJ.

Modulation of Nitro-Fatty Acid Signaling: Prostaglandin Reductase-1 is a Nitroalkene Reductase. J Biol. Chem. 2013 Aug 30;288(35):25626-37.

Salvatore SR, Vitturi DA, Baker PR, Bonacci G, Koenitzer JR, Woodcock SR, Freeman BA, Schopfer FJ.

Characterization and quantification of endogenous fatty acid nitroalkene metabolites in human urine. J. Lipid. Res. 2013 Jul;54(7):1998-2009.

Woodcock SR, Bonacci G, Gelhaus SL, Schopfer FJ.

Nitrated fatty acids: Synthesis and measurement. Free Radic. Biol. Med. 2013 Jun;59:14-26. 

Bonacci G, Baker PR, Salvatore SR, Shores D, Khoo NK, Koenitzer JR, Vitturi DA, Woodcock SR, Golin-Bisello F, Cole MP, Watkins S, St Croix C, Batthyany CI, Freeman BA, Schopfer FJ.

Conjugated Linoleic Acid is a Preferential Substrate for Fatty Acid Nitration. J. Biol. Chem. 2012 Dec 28;287(53):44071-82.

Bonacci G, Fletcher J, Devani M, Dwivedi H, Keller R, Chang C.

The cytoplasmic tyrosine kinase Arg regulates gastrulation via control of actin organization. Dev. Biol. 2012 Apr 1;364(1):42-55. Jan 18.

Bonacci G., Asciutto EK., Woodcock SR., Salvatore S., Freeman BA., and Schopfer FJ.

Gas-phase fragmentation analysis of nitro-fatty acids. J. Am. Soc. Mass Spectrom. 2011 22(9):1534-1551.

Bonacci G, Schopfer FJ, Batthyany CI, Rudolph TK, Rudolph V, Khoo NK, Kelley EE, Freeman BA.

Electrophilic Fatty acids regulate matrix metalloproteinase activity and expression.

J. Biol. Chem. 2011 May 6;286(18):16074-81.

Kansanen E, Bonacci G, Schopfer FJ, Kuosmanen SM, Tong KI, Leinonen H, Woodcock SR, Yamamoto M, Carlberg C, Ylä-Herttuala S, Freeman BA, Levonen AL.

Electrophilic Nitro-fatty Acids Activate Nrf2 by a Keap1 Cysteine 151-independent Mechanism. J Biol Chem. 2011 Apr 22;286(16):14019-27.

Cáceres LC, Bonacci G, Sánchez MC, Chiabrando GA.

Activated alpha2 macroglobulin induces matrix metalloproteinase 9 expression by low density lipoprotein receptor-related protein 1 through MAPK-ERK1/2 and NF-kappaB activation in macrophage derived cell lines. J. Cell. Biochem. 2010 Oct 15;111(3):607-17

Groeger AL, Cipollina C, Cole MP, Woodcock SR, Bonacci G, Rudolph TK, Rudolph V, Freeman BA, Schopfer FJ.

Cyclooxygenase-2 generates anti-inflammatory mediators from omega-3 fatty acids.

Nat. Chem. Biol. 2010 Jun;6(6):433-41.

Rudolph TK, Rudolph V, Edreira MM, Cole MP, Bonacci G, Schopfer FJ, Woodcock SR, Franek A, Pekarova M, Khoo NK, Hasty AH, Baldus S, Freeman BA.

Nitro-fatty acids reduce atherosclerosis in apolipoprotein e-deficient mice. Arterioscler. Thromb. Vasc. Biol. 2010 May;30(5):938-45.

Schopfer FJ, Cole MP, Groeger AL, Chen CS, Khoo NK, Woodcock SR, Golin-Bisello F, Motanya UN, Li Y, Zhang J, Garcia-Barrio MT, Rudolph TK, Rudolph V, Bonacci G, Baker PR, Xu HE, Batthyany CI, Chen YE, Hallis TM, Freeman BA.

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):12321-33.

Rudolph V, Rudolph TK, Schopfer FJ, Bonacci G, Woodcock SR, Cole MP, Baker PR, Ramani R, Freeman BA.

Endogenous generation and protective effects of nitro-fatty acids in a murine model of focal cardiac ischaemia and reperfusion. Cardiovasc. Res. 2010 Jan 1;85(1):155-66.

Schopfer FJ, Batthyany C, Baker PR, Bonacci G, Cole MP, Rudolph V, Groeger AL, Rudolph TK, Nadtochiy S, Brookes PS, Freeman BA.

Detection and quantification of protein adduction by electrophilic fatty acids: mitochondrial generation of fatty acid nitroalkene derivatives. Free Radic. Biol. Med. 2009 May 1;46(9):1250-9.

Rudolph V, Schopfer FJ, Khoo NK, Rudolph TK, Cole MP, Woodcock SR, Bonacci G, Groeger A, Golin-Bisello F, Chen CS, Baker PR, Freeman BA.

Nitro-fatty acid metabolome: saturation, desaturation, beta-oxidation and protein adduction. J. Biol. Chem. 2008 Nov 17.

Kelley EE, Batthyany CI, Hundley NJ, Woodcock SR, Bonacci G, Del Rio JM, Schopfer FJ, Lancaster JR Jr, Freeman BA, Tarpey MM.

Nitro-oleic Acid, a novel and irreversible inhibitor of Xanthine oxidoreductase. J. Biol. Chem. 2008; Dec 26;283(52):36176-84.

Bonacci G.; Caceres L.; Sanchez MC.; Chiabrando GA.

Activated alpha2-macroglobulin induces cell proliferation and mitogen-activated protein kinase activation by LRP-1 in the J774 macrophage-derived cell line. Arch. Biochem. Biophys. 2007 Apr 1;460(1):100-6

Chiabrando G.; Bonacci G.; Sanchez C.; Ramos A.; Zalazar F.; Vides MA.

A procedure for human Pregnancy Zone Protein (and human α2-Macroglobulin) purification using Hidrophobic Interaction Chromatography on Phenyl-Sepharose CL-4B Column. Protein Expr. Purif. 1997; 9: 399-406.