Differential Apoptotic and Mitogenic Effects of Lectins in Zebrafish

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.

Reprograming of Gene Expression of Key Inflammatory Signaling Pathways in Human Peripheral Blood Mononuclear Cells by Soybean Lectin and Resveratrol

“…Lectins (LEC) are used as natural plant insecticides. When consumed by people, they trigger immune responses in people depending on the dose [ 56 , 57 , 58 , 59 , 60 , 61 ]. Lectins are present in abundant amounts in soybeans, red kidney beans, red hot peppers, potatoes, tomatoes, wheat germ, eggplant, nuts, raw unpasteurized milk, and mother’s breast milk.…”

“…Most lectins are relatively heat-resistant to temperatures up to 70° C and rigorous heating conditions are required for their inactivation. Lectins present in soybeans, wheat grains (1 wheat grain has 10 μg of lectin), peppers, milk, and tomatoes are routinely consumed by people worldwide [ 56 , 57 , 58 , 59 , 60 , 61 ]. Our study has shown that LEC10 and LEC50 robustly induced gene expression of PSMB8 (LMP7), and most inflammatory cytokines like LPS (a potent prototype and proinflammatory agonist, which induces both innate and acquired immunity) as described below ( Figure 5 A–D).…”

An Update of Lectins from Marine Organisms: Characterization, Extraction Methodology, and Potential Biofunctional Applications

“…The biological significance of the isolated lectins in various marine organisms has not been fully elucidated, and investigations are currently ongoing [ 14 ]. Nevertheless, their roles in aquatic animals (i.e., reproduction, defense against pathogenic microbes (immunity), polyspermy block, morphogenesis and embryogenesis) are well studied [ 15 , 16 , 17 ]. The major classes of lectins identified in marine animals are C-type lectins (CTLs), F-type lectins (FTLs), X-type lectins (XTL), galectins (formerly S-type lectins), and pentraxins (P-type lectins) [ 6 , 18 ].…”

Review: Glucose-sensitive insulin

“…The applied polymers were hardly suited for pharmaceutical use (non-biodegradable Sepharose). Furthermore, ConA is notoriously toxic (mitogenic) [ 36 , 37 ], so ConA is not relevant for drug use. Although PEGylation of ConA was later pursued, this approach will not mitigate the issue of toxicity [ 38 ].…”