Molecular aspects of the energetic metabolism in the brain of birds, mice and ruminants - quantification of the genetic expression of key proteins of the glucose metabolism. Species analysis - specific path

• Grant number: 04/03170-5
• Support Opportunities: Research Projects - Thematic Grants
• Start date: October 01, 2005
• End date: September 30, 2009
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Marcelo de Cerqueira César
• Grantee: Marcelo de Cerqueira César
• Host Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
• Associated scholarship(s): 09/06687-2 - Proteomic study of apoptosis in avian neurons: the role of VDAC 1 and VDAC 2, BP.MS

Abstract

Recent results from our lab showed that there are two binding sites (A and B) of hexokinase to brain mitochondria, according to release with glucose-6-P (Cerqueira César and Wilson, 2002). The ratio A:B sites varied in a species - specific way. It was 90% A: 10% B in rat brain and 60% A: 40% B in rabbit and bovine brain, respectively. Later we detected that this species - specific variation, was due to differences in expression of VDAC isoforms (voltage dependent anion channel). VDAC 1 ans VDAC 2 were more expressed in bovine brain in comparison with rat brain (Cerqueira César and Wilson, 2004). Results from our lab that relative to the mRNA for VDAC 3, mRNAs for both VDAC 1 and VDAC 2 were more highly expressed in bovine brain than in rat brain (Cerqueira César and Wilson, 2004). Our results, with those from Shinohara et al. (2000) were the first to do a comparative quantitation between mRNA levels of the different VDAC isoforms in tissues from different species. The theory we are proposing is that there is a relationship between blood glucose levels and the species - specific expression of A and B hexokinase binding sites to brain mitochondria. Another purpose of this study is to determine a possible species - specific differential expression of VDAC, hexokinase and glucose transporters (GLUT). The biological tissues we are going to study are brain tissues from bovine (57 mg/dl blood glucose levels), rat (73 mg/dl) and chicken (168 mg/dl). We are looking for brain molecular adaptations to survive with low (bovine) and high blood glucose (chicken) and suggest molecular therapies for hiperglicemic ou hipoglicemic diseases in humans and monogastrics. Add to that the understanding of VDAC - hexokinase interaction is highly important, because it is a key point of apoptosis control. The proapoptotic protein Bax and hexokinase compete by the same mitochondrial binding site. Proteomic analysis by mass spectrometry will be done at the Thomson laboratory of mass spectrometry (UNICAMP) in cooperation with Prof. Marcos Eberlin. We will be looking for the identification of VDAC isoforms in chicken, bovine and rat brain. (AU)

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)

POLETI, MIRELE DAIANA; TESCH, ANDREA CRISTINA; CREPALDI, CARLA ROSSINI; MARTINS FERREIRA SOUZA, GUSTAVO HENRIQUE; EBERLIN, MARCOS NOGUEIRA; CESAR, MARCELO DE CERQUEIRA. Relationship Between Expression of Voltage-Dependent Anion Channel (VDAC) Isoforms and Type of Hexokinase Binding Sites on Brain Mitochondria. JOURNAL OF MOLECULAR NEUROSCIENCE, v. 41, n. 1, p. 48-54, MAY 2010. (04/03170-5)