Proteomic as a tool to understand HDL function and composition

• Grant number: 16/00696-3
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: August 01, 2017
• End date: July 31, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Graziella Eliza Ronsein
• Grantee: Graziella Eliza Ronsein
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 21/14715-8 - Investigating the interaction between high-density lipoprotein and endothelial cells, BP.IC; 21/12886-0 - Development of an analytical methodology to evaluate the modulation role of HDL in activated macrophages, BP.IC; 19/25702-4 - Understanding the effects of high density lipoprotein on human macrophages, BP.DD; + associated scholarships 19/12994-7 - Development of an analytical methodology to evaluate the ability of HDL to deliver cholesterol ester to hepatic cells, BP.IC; 18/26516-7 - Development of an analytical methodology to evaluate the role of HDL in activated macrophages, BP.IC; 17/17270-1 - Study of the effect of HDL on activated neutrophils, BP.DD - associated scholarships

Abstract

The inverse relationship between the levels of HDL cholesterol (HDL-C) and the risk of cardiovascular disease has been established for a long time. However, clinical trials that pharmacologically elevate HDL-C showed no clinical benefits. The HDL metric used by clinical laboratories - the amount of cholesterol - is limited, since it does not provide information about composition (except cholesterol content) and function of HDL. Evidence obtained with cellular and animal models and in humans support the proposal that HDL can be converted to a dysfunctional particle with significant impairment of its protective roles. However, the causes and mechanisms of this transformation remain poorly understood. The purpose of this proposal is to identify the mechanisms that promote the formation of dysfunctional HDL and the cellular consequences of this transformation. To achieve this goal will be used multiple approaches, starting with cell models especially developed to assess the functionality of HDL. Preliminary results demonstrated that lipoproteins lose their functions in a dyslipidemic environment. In this way, using an animal model of hyperlipidemia and insulin resistance, we will search for proteins with altered expression and abundance in the lipoproteins of these animals and correlate these quantitative proteomics data with functional studies. Moreover, these studies will be extended to patients with Type 2 Diabetes who have diabetic dyslipoproteinemia, a condition characterized by low levels of HDL-C and high levels of triglycerides. Through shotgun and quantitative proteomics, we will look for biomarkers of dysfunctionality in lipoproteins of these patients, and correlate these findings with functional studies. Our studies can promote a significant advance in the understanding of the pathways that make the lipoproteins dysfunctional in dyslipidemias. (AU)

Scientific publications

(17)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SILVA, AMANDA R. M.; TOYOSHIMA, MARCOS T. K.; PASSARELLI, MARISA; DI MASCIO, PAOLO; RONSEIN, GRAZIELLA E.. Comparing Data-Independent Acquisition and Parallel Reaction Monitoring in Their Abilities To Differentiate High-Density Lipoprotein Subclasses. JOURNAL OF PROTEOME RESEARCH, v. 19, n. 1, p. 248-259, JAN 2020. (17/07725-1, 16/00696-3, 13/07937-8)

NASCIMENTO, RAFAELA OLIVEIRA; PRADO, FERNANDA MANSO; MASSAFERA, MARIANA PEREIRA; DI MASCIO, PAOLO; RONSEIN, GRAZIELLA ELIZA. Dehydromethionine is a common product of methionine oxidation by singlet molecular oxygen and hypohalous acids. Free Radical Biology and Medicine, v. 187, p. 12-pg., 2022-07-01. (16/00696-3, 12/12663-1)

JAYME, STELLA BOUTRIS; PRADO, FERNANDA MANSO; MASSAFERA, MARIANA PEREIRA; RONSEIN, GRAZIELLA ELIZA; DI MASCIO, PAOLO. Characterization and Quantification of Tryptophan- and Tyrosine-derived Hydroperoxides(dagger). Photochemistry and Photobiology, v. 98, n. 3, p. 9-pg., 2022-04-28. (13/07937-8, 16/00696-3, 12/12663-1)

PAVIANI, VERONICA; DE MELO, PAULO JUNQUEIRA; AVAKIN, AMARYLLIS; DI MASCIO, PAOLO; RONSEIN, GRAZIELLA ELIZA; AUGUSTO, OHARA. Human cataractous lenses contain cross-links produced by crystallin-derived tryptophanyl and tyrosyl radicals. Free Radical Biology and Medicine, v. 160, p. 356-367, NOV 20 2020. (16/00696-3, 13/07937-8)

VALERIO, HELLEN PAULA; RAVAGNANI, FELIPE GUSTAVO; CANDELA, ANGELA PAOLA YAYA; DA COSTA, BRUNA DIAS CARVALHO; RONSEIN, GRAZIELLA ELIZA; DI MASCIO, PAOLO. Spatial proteomics reveals subcellular reorganization in human keratinocytes exposed to UVA light. ISCIENCE, v. 25, n. 4, p. 27-pg., 2022-04-15. (15/07768-7, 16/00696-3, 16/11430-4, 12/12663-1, 13/07937-8)

SOUZA JUNIOR, DOUGLAS RICARDO; SILVA, AMANDA RIBEIRO MARTINS; RONSEIN, GRAZIELLA ELIZA. Strategies for consistent and automated quantification of HDL proteome using data-independent acquisition. Journal of Lipid Research, v. 64, n. 7, p. 14-pg., 2023-07-03. (17/07725-1, 16/00696-3, 13/07937-8, 19/25702-4)

SANTANA, MONIQUE F. M.; LIRA, AECIO L. A.; PINTO, RAPHAEL S.; MINANNI, CARLOS A.; SILVA, AMANDA R. M.; SAWADA, MARIA I. B. A. C.; NAKANDAKARE, EDNA R.; CORREA-GIANNELLA, MARIA L. C.; QUEIROZ, MARCIA S.; RONSEIN, GRAZIELLA E.; et al. Enrichment of apolipoprotein A-IV and apolipoprotein D in the HDL proteome is associated with HDL functions in diabetic kidney disease without dialysis. LIPIDS IN HEALTH AND DISEASE, v. 19, n. 1, p. 14-pg., 2020-09-14. (16/00696-3, 18/00172-0, 17/07725-1, 16/15603-0, 15/21072-5)

HE, YI; RONSEIN, GRAZIELLA E.; TANG, CHONGREN; JARVIK, GAIL P.; DAVIDSON, W. SEAN; KOTHARI, VISHAL; SONG, HYUN D.; SEGREST, JERE P.; BORNFELDT, KARIN E.; HEINECKE, JAY W.. Diabetes Impairs Cellular Cholesterol Efflux From ABCA1 to Small HDL Particles. Circulation Research, v. 127, n. 9, p. 1198-1210, OCT 9 2020. (16/00696-3)

RONSEIN, GRAZIELLA E.; VAISAR, TOMAS; DAVIDSON, W. SEAN; BORNFELDT, KARIN E.; PROBSTFIELD, JEFFREY L.; O'BRIEN, KEVIN D.; ZHAO, XUE-QIAO; HEINECKE, JAY W.. Niacin Increases Atherogenic Proteins in High-Density Lipoprotein of Statin-Treated Subjects. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, v. 41, n. 8, p. 2330-2341, AUG 2021. (16/00696-3)

VALERIO, HELLEN PAULA; RAVAGNANI, FELIPE GUSTAVO; RONSEIN, GRAZIELLA ELIZA; DI MASCIO, PAOLO. A single dose of Ultraviolet-A induces proteome remodeling and senescence in primary human keratinocytes. SCIENTIFIC REPORTS, v. 11, n. 1, DEC 2 2021. (15/07768-7, 13/07937-8, 12/12663-1, 16/11430-4, 16/00696-3)

SOUZA JUNIOR, DOUGLAS RICARDO; MARTINS SILVA, AMANDA RIBEIRO; ROSA-FERNANDES, LIVIA; REIS, LORENNA ROCHA; ALEXANDRIA, GABRIELLY; BHOSALE, SANTOSH D.; GHILARDI, FABIO DE ROSE; DALCOQUIO, TALIA FALCAO; BERTOLIN, ADRIADNE JUSTI; NICOLAU, JOSE CARLOS; et al. HDL proteome remodeling associates with COVID-19 severity. JOURNAL OF CLINICAL LIPIDOLOGY, v. 15, n. 6, p. 796-804, NOV-DEC 2021. (15/26722-8, 16/00696-3, 20/04923-0, 19/25702-4, 17/07725-1, 18/15549-1, 18/18257-1, 13/07937-8)

RONSEIN, GRAZIELLA ELIZA; VAISAR, TOMAS. Deepening our understanding of HDL proteome. EXPERT REVIEW OF PROTEOMICS, v. 16, n. 9, AUG 2019. (16/00696-3, 13/07937-8)

HOLZER, MICHAEL; LJUBOJEVIC-HOLZER, SENKA; SOUZA JUNIOR, DOUGLAS RICARDO; STADLER, JULIA T.; RANI, ALANKRITA; SCHARNAGL, HUBERT; RONSEIN, GRAZIELLA ELIZA; MARSCHE, GUNTHER. HDL Isolated by Immunoaffinity, Ultracentrifugation, or Precipitation is Compositionally and Functionally Distinct. Journal of Lipid Research, v. 63, n. 12, p. 13-pg., 2022-12-05. (13/07937-8, 16/00696-3)

NASCIMENTO, RAFAELA OLIVEIRA; PRADO, FERNANDA MANSO; GENNARI DE MEDEIROS, MARISA HELENA; RONSEIN, GRAZIELLA ELIZA; DI MASCIO, PAOLO. Singlet Molecular Oxygen Generation in the Reaction of Biological Haloamines of Amino Acids and Polyamines with Hydrogen Peroxide(dagger). Photochemistry and Photobiology, v. N/A, p. 11-pg., 2022-09-26. (12/12663-1, 13/07937-8, 16/00696-3)

DI MASCIO, PAOLO; MARTINEZ, GLAUCIA R.; MIYAMOTO, SAYURI; RONSEIN, GRAZIELLA E.; MEDEIROS, MARISA H. G.; CADET, JEAN. Singlet Molecular Oxygen Reactions with Nucleic Acids, Lipids, and Proteins. CHEMICAL REVIEWS, v. 119, n. 3, p. 2043-2086, FEB 13 2019. (13/07937-8, 16/00696-3, 12/12663-1)

SUA-CESPEDES, CRISTHIAN; LACERDA, JOSE THALLES; ZANETTI, GIOVANNA; DAVID, DANIELA DANTAS; MORAES, MARIA NATHALIA; DE ASSIS, LEONARDO V. M.; CASTRUCCI, ANA MARIA L.. Melanopsin (OPN4) is a novel player in skin homeostasis and attenuates UVA-induced effects. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, v. 242, p. 15-pg., 2023-04-03. (16/00696-3, 13/07937-8, 19/19005-9, 21/01659-2, 17/26651-9, 18/23043-0, 18/16511-8, 12/50214-4, 12/12663-1, 18/14728-0, 17/24615-5, 20/04524-8, 14/16412-9)

REIS, LORENNA ROCHA; JUNIOR, DOUGLAS RICARDO SOUZA; TOMASIN, REBEKA; BRUNI-CARDOSO, ALEXANDRE; DI MASCIO, PAOLO; RONSEIN, GRAZIELLA ELIZA. Citrullination of actin-ligand and nuclear structural proteins, cytoskeleton reorganization and protein redistribution across cellular fractions are early events in ionomycin-induced NETosis. REDOX BIOLOGY, v. 64, p. 14-pg., 2023-06-23. (13/07937-8, 16/00696-3, 17/17270-1, 19/25702-4)