Differential Apoptotic and Mitogenic Effects of Lectins in Zebrafish.

Kaidi Wang,Kangsen Mai,Huihui Zhou,Chengdong Liu,Yiying Hou,Xuan Wang,Gen He

doi:10.3389/fendo.2019.00356

Abstract

Plant lectins represent a major group of anti-nutritional factors that can be toxic to human and animals. However, the mechanisms by which lectins regulate cell fates are not well-understood. In the present study, the cellular and molecular impacts of three common lectins, agglutinins from wheat germ [wheat germ agglutinin (WGA)], soybean [soybean agglutinin (SBA)], and peanut [peanut agglutinin (PNA)] were examined in zebrafish embryo and liver cells. WGA and SBA were found to induce cell apoptosis both in vitro and in vivo, while PNA stimulated cell proliferation. WGA and SBA reduced levels of B cell lymphoma-2 (Bcl-2), phosphorylation of Bcl-2-associated death promoter (Bad), cyclin-dependent kinase 4 (Cdk4), and phosphorylation of the retinoblastoma (Rb). WGA and SBA also inhibited the activities of cell survival pathways including protein kinase B (Akt), extracellular signal-regulated protein kinases 1 and 2 (Erk1/2), and target of rapamycin (Tor). Furthermore, WGA and SBA shifted the cellular metabolism characterized by reduced expression of glucose-6-phosphate dehydrogenase (g6pd) and increased expression of glutamine synthetase (glul) and glutamate dehydrogenase (glud). However, PNA showed the opposite effects toward these molecular markers compared to those of WGA and SBA. Therefore, our results revealed some plant lectins (WGA and SBA) were toxic while the other (PNA) was mitogenic. Further characterization of the distinct functions of individual lectins should be valuable for both nutrition and other potential applications.

Highlights

Lectins are carbohydrate binding proteins found in most plants and can act as a major anti-nutritional factor (ANF) that decrease the bioavailability of nutrients and cause adverse physiological effects in animals [1,2,3]
After cells were treated with wheat germ agglutinin (WGA) at 100 μg/ml, the apoptotic ratio was raised from 5.5 ± 0.8 to 45.4 ± 0.8%
B cell lymphoma-2 (Bcl-2) protein avoids the collapse of the mitochondrial transmembrane potential and inhibits the release of cytochrome c, prevents the activation of downstream caspase cascade that occurs during apoptosis [40, 41], while un-phosphorylated Bcl-2-associated death promoter (Bad) binds to and inactivates Bcl-2, initiates apoptosis

Summary

Introduction

Lectins are carbohydrate binding proteins found in most plants and can act as a major anti-nutritional factor (ANF) that decrease the bioavailability of nutrients and cause adverse physiological effects in animals [1,2,3]. Some lectins are known to be very resistant to common digestive proteases and not degraded during their passage through the digestive tract [9]. They can be taken up into the intestinal epithelial cells and transported throughout the body [9, 10]. An appreciable portion of lectins, such as WGA (wheat germ agglutinin) and SBA is transported across the gut wall and cause systemic effects through circulation in rats [14, 15]. Disrupted hormonal and metabolic homeostasis was proposed as causative reasons in rats [19], but the exact mechanisms are not clear

Objectives

Methods

Results

Conclusion