Cell metabolism and mitochondrial dynamics in kidney ischemia-reperfusion injury: a role for heme oxygenase 1

• Grant number: 18/21844-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2018
• End date: November 30, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Nathalia Franchon Marques Tejada
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 17/05264-7 - Cell metabolism, microbiota and immune system: new paradigms in renal diseases physiopathology, AP.TEM

Abstract

Kidney transplantation is one of the most performed currently. Nonetheless, despite few organ availability patient outcomes depends also of how long the kidney remained in ischemia, both warm, due to blood flow privation in vivo, and cold, during organ transportation. These conditions lead to metabolic and mitochondrial dysfunctions related to cell damage and delayed graft function (DGF). Hence, we suppose that interventions with drugs capable to modify cell metabolism and mitochondrial dynamics could ensure better organ preservation and function. In this context, we intend to study heme-oxygenase-1, a compound that had already some benefic roles reported in kidney ischemia and transplantation scopes, as cytoprotection, metabolic modulation, and mitochondria preservation. To accomplish this, we will employ three experimental conditions: (I) mice treated with hemin, a HO-1 inductor, 24h before a ischemia-reperfusion injury (II) mice treated with hemin 24h before a nephrectomy, followed by kidney storage in a cold preservation solution (III) untreated mice submitted to a nephrectomy, and kidney storage in a cold preservation solution with hemin. In kidney tissues, we will analyze glucose and lactate levels through colorimetric tests; genes and proteins related to mitochondrial fusion and fission with qPCR and western blot, respectively; mitochondrial superoxide release using Mitosox; mitochondrial structure by electronic microscopy and mitochondrial function and mass employing Mitotraker and TMRE probes. Our hypothesis is that HO-1 administration in these experimental conditions will trigger a metabolic improvement and an appropriate balance between mitochondria fusion and fission, conditions associated to a better graft fuction.

Scientific publications

(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)

TEJADA, NATHALIA FRANCHON MARQUES; LOPES, JOAO VITOR ZIROLDO; DA GONCALVES, LUIS EDUARDO DUARTE; DA CONCEICAO, IZABELA MAMEDE COSTA ANDRADE; FRANCO, GLORIA REGINA; GHIROTTO, BRUNO; CAMARA, NIELS OLSEN SARAIVA. AIM2 as a putative target in acute kidney graft rejection. FRONTIERS IN IMMUNOLOGY, v. 13, p. 15-pg., 2022-09-30. (19/22409-4, 18/21844-6, 17/05264-7)