A speciomic toolkit to investigate fatty acid-mediated changes in plasma zinc speciation and their physiological effects

• Grant number: 20/08543-7
• Support Opportunities: Regular Research Grants
• Start date: January 01, 2022
• End date: December 31, 2024
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Analytical Chemistry
• Agreement: BBSRC, UKRI
• Principal Investigator: Marco Aurelio Zezzi Arruda
• Grantee: Marco Aurelio Zezzi Arruda
• Principal researcher abroad: James Alan Stewart
• Institution abroad: University of St Andrews, Scotland
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Carlos Henrique Inacio Ramos ; Claudia Andrea Blindauer
• Associated scholarship(s): 24/02461-0 - Cell culture and its analysis via single-cell ICP-MS, BP.TT; 23/09289-5 - Cell culture and their analysis via single-cell ICP-MS, BP.TT

Abstract

Our work has shown that an allosteric relationship exists between circulatory non-esterified fatty acid (NEFA) transport and plasma zinc handling through binding to human serum albumin (HSA). This suggests that plasma zinc speciation is influenced by NEFAs in disease states in a manner that impacts upon circulatory processes, including coagulation and insulin signalling. We will examine how binding of (patho)physiologically relevant mixtures of NEFAs alter zinc binding to HSA using ITC. We will assess how NEFAs influence plasma zinc speciation using an established approach incorporating 2D-PAGE combined with LA-ICP-MS, which will be further developed to include additional separation and analysis techniques. We will also develop a bespoke approach incorporating bidimensional separation with quantitative MS and ICP-MS to assess NEFA-induced speciation changes. The zinc-binding properties of the most interesting proteins identified will be probed using ITC, ESI-MS and IMMS analyses. The effect of NEFA-induced changes in the zinc-binding properties of HSA on insulin pharmacodynamics will be assessed using a FRET-based approach. Zinc flux in primary HUVECs will be measured using an established stable Zn isotope-based method to determine how NEFAs influence cellular zinc homeostasis, with intracellular speciation examined using the 2D-PAGE/LA-ICP-MS. Combining these approaches will enable us to identify proteins that bind zinc as the net flux into the cell increases in response to NEFAs. Finally, we will examine how NEFAs influence insulin signalling in HUVECs. Activation of specific downstream pathways will be assessed using specific antibodies, qPCR and luciferase assays. (AU)

Scientific publications

(8)

(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)

ARRUDA, MARCO AURELIO ZEZZI; JESUS, JEMMYSON ROMARIO DE; BLINDAUER, CLAUDIA ANDREA; STEWART, ALAN JAMES. Speciomics as a concept involving chemical speciation and omics. JOURNAL OF PROTEOMICS, v. 263, p. 8-pg., 2022-07-15. (20/08543-7, 19/00018-3, 18/25207-0, 14/50867-3, 17/50085-3, 19/24445-8)

FREITAS, DANIEL CARNEIRO; MAZALI, ITALO ODONE; SIGOLI, FERNANDO APARECIDO; FRANCISCHINI, DANIELLE DA SILVA; ARRUDA, MARCO AURELIO ZEZZI. The microwave-assisted synthesis of silica nanoparticles and their applications in a soy plant culture. RSC ADVANCES, v. 13, n. 39, p. 9-pg., 2023-09-08. (19/24445-8, 19/00063-9, 14/50906-9, 14/50867-3, 19/00018-3, 21/06326-1, 18/25207-0, 20/08543-7)

CHACON-MADRID, KATHERINE; FRANCISCHINI, DANIELLE DA SILVA; ARRUDA, MARCO AURELIO ZEZZI. The role of silver nanoparticles effects in the homeostasis of metals in soybean cultivation through qualitative and quantitative laser ablation bioimaging. JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY, v. 79, p. 7-pg., 2023-05-22. (17/50085-3, 19/24445-8, 19/00063-9, 14/50867-3, 18/25207-0, 20/08543-7)

SILVA, ANA BEATRIZ SANTOS DA; ARRUDA, MARCO AURELIO ZEZZI. Single-cell ICP-MS to address the role of trace elements at a cellular level. JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY, v. 75, p. 15-pg., 2023-01-01. (18/25207-0, 14/50867-3, 20/06934-9, 20/08543-7, 19/24445-8)

DE JESUS, JEMMYSON R.; LINHARES, LEONARDO A.; ARAGA, ANNELIZE Z. B.; ARRUDA, MARCO A. Z.; RAMOS, CARLOS H. I.. The stability and function of human cochaperone Hsp40/DNAJA1 are affected by zinc removal and partially restored by copper. Biochimie, v. 213, p. 7-pg., 2023-05-30. (17/26131-5, 19/24445-8, 14/50867-3, 18/00768-0, 18/25207-0, 20/08543-7)

ARRUDA, MARCO AURELIO ZEZZI; DA SILVA, ANA BEATRIZ SANTOS; KATO, LILIAN SEIKO. There Is Plenty of Room in Plant Science: Nanobiotechnology as an Emerging Area Applied to Somatic Embryogenesis. Journal of Agricultural and Food Chemistry, v. N/A, p. 7-pg., 2023-02-14. (19/24445-8, 18/25207-0, 19/00018-3, 20/06934-9, 20/08543-7, 14/50867-3, 17/50085-3, 21/15218-8)

SILVA, ANA BEATRIZ SANTOS DA; ARRUDA, MARCO AURELIO ZEZZI. Exploring single-particle ICP-MS as an important tool for the characterization and quantification of silver nanoparticles in a soybean cell culture. SPECTROCHIMICA ACTA PART B-ATOMIC SPECTROSCOPY, v. 203, p. 9-pg., 2023-03-27. (19/24445-8, 20/06934-9, 14/50867-3, 18/25207-0, 20/08543-7)

DA COSTA, LUANA FERREIRA; ZEZZI ARRUDA, MARCO AURELIO. Simultaneous Hydride Generation Inductively Coupled Plasma Mass Spectrometry for the Evaluation of Different Generations of Soybean Seeds. BRAZILIAN JOURNAL OF ANALYTICAL CHEMISTRY, v. 10, n. 39, p. 11-pg., 2023-04-01. (17/50085-3, 19/24445-8, 14/50867-3, 19/00018-3, 18/25207-0, 20/08543-7)