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

Author(s)

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

• Document type: Journal article
• Source: FOOD & FUNCTION; v. 13, n. 24, p. 19-pg., 2022-11-30.

Abstract

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)

• FAPESP's process: 18/26584-2 - Effect of citrus flavanones in Min6 cells under oxidative stress: Proteomic approach
• Grantee: Sara Lima Anacleto
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• FAPESP's process: 18/03965-0 - Citrus Flavanones- mechanisms of protection of pancreatic-beta cells under oxidative stress
• Grantee: Sara Lima Anacleto
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 13/07914-8 - FoRC - Food Research Center
• Grantee: Bernadette Dora Gombossy de Melo Franco
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC