PROTEIN SUCCINYLATION AND MALONYLATION: PROFILES IN SCHIZOPHRENIA AND ANTIPSYCHOTIC USE

Bradley Joseph Smith; Caroline Brandão-Teles; Giuliana da Silva Zuccoli; Guilherme Reis de Oliveira; Mariana Fioramonte; Verônica M. Saia-Cereda; Daniel Martins de Souza

Todos os Trabalhos

Trabalho

Título do Trabalho

PROTEIN SUCCINYLATION AND MALONYLATION: PROFILES IN SCHIZOPHRENIA AND ANTIPSYCHOTIC USE

Autores

Bradley Joseph Smith
Caroline Brandão-Teles
Giuliana da Silva Zuccoli
Guilherme Reis de Oliveira
Mariana Fioramonte
Verônica M. Saia-Cereda
Daniel Martins de Souza

Modalidade

Apresentação de Pôster

Área temática

Bioinformática

Data de Publicação

09/06/2023

País da Publicação

Brasil

Idioma da Publicação

Inglês

Página do Trabalho

https://www.even3.com.br/anais/v-gbmeeting/608495-protein-succinylation-and-malonylation--profiles-in-schizophrenia-and-antipsychotic-use

ISBN

978-85-5722-785-9

Palavras-Chave

succinylation, malonylation, schizophrenia, antipsychotics, biomarkers, post-translational modifications, shotgun proteomics

Resumo

Introduction: Lysine is a versatile amino acid that can be the target of many post-translational modifications (PTMs). Such PTMs include succinylation and malonylation, two PTMs with intrinsic relations to energy metabolism, starting with their precursors: succinyl-CoA and malonyl-CoA, and progressing to their high prevalence on mitochondrial and metabolic proteins. Since many multifactorial diseases, including schizophrenia, are known to have dysregulated energy metabolism, studying these modification profiles can provide insight into another layer of biological regulation to understand their etiology, progression, and treatment. Methods: Several datasets from 1D and 2D liquid chromatography-mass spectrometry were reanalyzed in silico for succinylated and malonylated proteins. These datasets consisted of postmortem brain tissue from patients with schizophrenia and controls, mitochondrial enrichments of these tissues, and human oligodendrocytes in culture. The glutamate hypothesis-based schizophrenia model MK-801, three antipsychotics, and co-treatments were studied in cell cultures. The peptides were quantified with label-free quantitation, and bioinformatic tools extracted site-based data and affected biological pathways. Results: The levels of several hundred modified peptides were found to be dysregulated in response to antipsychotics, varying between each. Biologically interesting proteins also exhibited an attenuated profile in MK-801/antipsychotic cotreatments. Postmortem brain regions showed differences in global modification profiles in both number and direction of dysregulation, with biological pathway enrichment by the dysregulated, modified proteins. Conclusions: This is the first known study to investigate malonylation in the context of neurological disorders or their treatment, and very few have begun investigations into succinylation in this context. It serves as proof-of-concept that these PTMs respond to both internal and external stimuli, highlighting the need for continued study. Changes in modification can be studied as potential biomarkers for schizophrenia and its treatment, as well as highlight otherwise unseen modulations in biological pathways that are altered in disease or related to medication side effects.

Título do Evento: V GBMeeting
Cidade do Evento: Campinas
Título dos Anais do Evento: Anais do GBMeeting: Encontro Anual da Pós Graduação em Genética e Biologia Molecular da UNICAMP
Nome da Editora: Even3
Meio de Divulgação: Meio Digital
DOI: Obter o DOI

Como citar

SMITH, Bradley Joseph et al.. PROTEIN SUCCINYLATION AND MALONYLATION: PROFILES IN SCHIZOPHRENIA AND ANTIPSYCHOTIC USE.. In: Anais do GBMeeting: Encontro Anual da Pós Graduação em Genética e Biologia Molecular da UNICAMP. Anais...Campinas(SP) Unicamp, 2023. Disponível em: https//www.even3.com.br/anais/v-gbmeeting/608495-PROTEIN-SUCCINYLATION-AND-MALONYLATION--PROFILES-IN-SCHIZOPHRENIA-AND-ANTIPSYCHOTIC-USE. Acesso em: 27/07/2024