Citrus flavanone metabolites protect pancreatic beta-cells against cholesterol stress through a multi-proteomic mechanism

Autor(es)

Fraga, Layanne Nascimento ; Anacleto, Sara Lima ; Milenkovic, Dragan ; Lajolo, Franco Maria ; Aymoto Hassimotto, Neuza Mariko

• Tipo de documento: Artigo Científico
• Fonte: FOOD & FUNCTION; v. 13, n. 24, p. 19-pg., 2022-11-30.

Resumo

Citrus flavanones may improve oxidative stress and insulin resistance induced by western diets. However, there is a paucity of studies investigating the change in protein expression levels. This study evaluated the protection and the mechanisms of action of citrus flavanone metabolites, hesperetin 7-glucuronide (H7G) and 3-(4 '-hydroxyphenyl) propanoic acid (PA), on pancreatic beta-cell function under oxidative stress induced by cholesterol using the global proteomics approach. Cholesterol induced changes in the global proteomic profile in the pancreatic beta-cell line Min6. On the other hand, proteomics analysis identified 254 proteins differentially expressed with H7G and 352 with PA treatments, most of them were opposite to the changes induced by cholesterol. Bioinformatics analysis showed that these proteins are implicated in cell functions like cell signaling (insulin signaling, p30MAPK signaling, and others), metabolism (glucokinase and glutathione metabolisms), and inflammation pathways (TNF-alpha and NF-kappa B pathways). Also, the results of molecular docking suggest that H7G and PA could bind to putative transcription factors (PPAR-gamma, STAT-3, CREB1, NF-kappa B, NFYA) and cell signaling proteins (IKK, RAS, Pi3K, ERK), which results in changes in protein expression observed. Altogether, these data suggest that the treatment with H7G and PA protects pancreatic beta-cells against stress induced by cholesterol through multi-proteomic mechanisms of action. (AU)

• Processo FAPESP: 18/26584-2 - Efeito de flavanonas de citrus em células Min6 submetidas ao estresse oxidativo: abordagem proteômica
• Beneficiário: Sara Lima Anacleto
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Mestrado
• Processo FAPESP: 18/03965-0 - Flavanonas de Citrus- mecanismos de proteção de células beta-pancreáticas submetidas ao estresse oxidativo
• Beneficiário: Sara Lima Anacleto
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 13/07914-8 - FoRC - Centro de Pesquisa em Alimentos
• Beneficiário: Bernadette Dora Gombossy de Melo Franco
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs