5-Bromoprotocatechualdehyde Combats against Palmitate Toxicity by Inhibiting Parkin Degradation and Reducing ROS-Induced Mitochondrial Damage in Pancreatic β-Cells.

Seon-Heui Cha,Soo-Jin Heo,Hee-Sook Jun,Chunying Zhang

doi:10.3390/antiox10020264

Abstract

Pancreatic β-cell loss is critical in diabetes pathogenesis. Up to now, no effective treatment has become available for β-cell loss. A polyphenol recently isolated from Polysiphonia japonica, 5-Bromoprotocatechualdehyde (BPCA), is considered as a potential compound for the protection of β-cells. In this study, we examined palmitate (PA)-induced lipotoxicity in Ins-1 cells to test the protective effects of BPCA on insulin-secreting β-cells. Our results demonstrated that BPCA can protect β-cells from PA-induced lipotoxicity by reducing cellular damage, preventing reactive oxygen species (ROS) overproduction, and enhancing glucose-stimulated insulin secretion (GSIS). BPCA also improved mitochondrial morphology by preserving parkin protein expression. Moreover, BPCA exhibited a protective effect against PA-induced β-cell dysfunction in vivo in a zebrafish model. Our results provide strong evidence that BPCA could be a potential therapeutic agent for the management of diabetes.

Highlights

Published: 9 February 2021Diabetes mellitus (DM) is a group of chronic metabolic disorders diagnosed by high levels of blood sugar over a prolonged period of time and a consequent insulin deficiency.DM has become one of the most concerning diseases due to its association with several complications [1,2,3] and the rise in its global incidence (International Diabetes Federal, IDF diabetes atlas, seventh edition)
We found that P. japonica extract (PJE) showed prominent protective effects for β-cells, and one of its target standards was BPCA [35]
palmitic acid (PA)-induced β-cell apoptosis in the mitochondrial pathway was evaluated, and we provide evidence that BPCA upregulates anti-apoptotic Bcl-2 and downregulates pro-apoptotic Bax, cytochrome C, and cleavedcaspase-3 protein expression (Figure 2), suggesting that the combating effect of BPCA is associated with the mitochondrial pathway of PA-induced β-cell damage

Summary

Introduction

Published: 9 February 2021Diabetes mellitus (DM) is a group of chronic metabolic disorders diagnosed by high levels of blood sugar over a prolonged period of time and a consequent insulin deficiency.DM has become one of the most concerning diseases due to its association with several complications [1,2,3] and the rise in its global incidence (International Diabetes Federal, IDF diabetes atlas, seventh edition). Diabetes mellitus (DM) is a group of chronic metabolic disorders diagnosed by high levels of blood sugar over a prolonged period of time and a consequent insulin deficiency. The three major types of DM, i.e., type 1 diabetes (T1D), type 2 diabetes (T2D), and gestational diabetes, have different etiologies, they all feature a crucial pathological transition into hyperglycemia and a consequent overproduction of reactive oxygen species (ROS) [4]. ROS constitute a heterogeneous group of highly reactive molecules that includes free radicals, such as superoxide radicals, hydroxyl radicals, peroxyl radicals, and hydroperoxyl radicals, as well as non-radical species, such as hydrogen peroxide and hydrochloric acid [5,6]. Pancreatic β-cells are essential for the maintenance of glucose homeostasis and function by sensing the elevated blood glucose levels and subsequently producing the glucoselowering hormone insulin. Sufficient pancreatic β-cell mass and reserves are achieved through β-cell proliferation, which has a critical impact on long-term prevention of T2D [7]

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Conclusion