Soybean agglutinin (SBA) is an important anti-nutritional factor in soybean. SBA can induce animal growth inhibition, cause pathological changes of intestinal tissue, and decrease in the immune system functioning. Recently, a great deal of research has been done on the effects of SBA on cell morphology, division, apoptosis, autophagy, as well as the correlated signal transduction pathway. This review mainly covers the chemical and biological characteristics of SBA, describes the multifaceted aspects of SBA anti-nutritional functions, and highlights the possible cellular and molecular mechanism of anti-nutritional effects of SBA. This review has important implications for the prevention and treatment of SBA-induced diseases, drug development, processing techniques of plant products, prevention of food- borne toxins, as well as human and animal health protection.
Soybean agglutinin (SBA), also known as lectin, is a major anti-nutritional factor (ANF) in soybean seeds and products. Such substance represents about 10% of the total protein in mature soybean seeds. SBA can resist the enzymatic digestion and keep its biological activity throughout the entire intestinal tract due to its stability of the structure (
Therefore, the herein review aims to describe the main chemical and biological functions of SBA, describes the multifaceted aspects of SBA anti-nutritional functions, and highlights the anti-nutritional mechanisms of SBA. This review provides some help for the systematic understanding of the related progress of SBA.
SBA has a typical four-stage structure of legume agglutinin with a molecular weight of 120 kDa, an isoelectric point of 5.81, a sedimentation coefficient of 6.05, and sedimentation with 7S protein in ultracentrifugation.
SBA is composed of four subunits, each of which has a molecular weight of about 30 kDa. Each subunit has a covalently linked oligosaccharide chain containing 9 mannose and 2 N-phthaloyl-glucosamine (Man9GlcNAc2).
The sugar chain of each subunit in SBA is covalently linked with the amino-N of the 75th aspartame residue of the peptide chain (Asn-75) in the form of an N-glp-glucosamine bond. The sugar chain is located at the atypical interface of the subunit and interacts with the amino acid residue of the adjacent subunit. Each subunit of SBA also contains a closely bound Ca2+ and Mn2+ (
Based on the structure characteristic of SBA, it can form specific binding with N-acetyl-D-galactosamine or galactose (
Like other plant lectins, the basic biological function of SBA is to agglutinate animal red blood cells and promote cell division.
The understanding of SBA begun with its agglutination discovery. SBA possesses species-specific on erythrocyte agglutination activity (
Another biological activity of SBA is promoting mitogenic activity. SBA can promote lymphocyte division, and enrichment of erythroblasts (
As one of the main anti-nutritional factors in soybean, the content of SBA in mature soybean seeds is up to about 10% of the total protein. Although its biological activity can be removed by some appropriate methods (
In general, the effects of SBA on animal growth and health are mainly manifested in the inhibition of animal growth and development, the destruction of animal intestine structure and function, and the decrease of immune function.
SBA causes growth inhibition and negatively effects on animal health. The effects of SBA on the growth performance of animals vary with the animals’ age, species, and SBA dose (
The effect of SBA on monogastric animals was significantly greater than that on ruminants. This may be due to the fermentation of rumen microorganisms in ruminants, which reduces the biological activity of SBA. The effect of SBA on pigs was significantly greater than that on chickens. SBA in the diet can cause intestinal damage in piglets (
SBA can damage the brush border, reduce the surface area of intestinal absorption, and affect the digestion and absorption of nutrients (
After the damage of the intestinal structure caused by SBA, the nutrient digestive and absorptive capabilities are also damaged. SBA can significantly impact the transportation of macro-nutrients (most notably glucose and amino acids) through the intestinal membrane (
SBA can reduce the number of intestinal brush border epithelial cells, inhibit the activity of various enzymes (
A little amount of SBA in a normal diet may decrease the trypsin activity and increase the amylase activity of amylase in the pancreatic juice (
SBA can induce a local inflammatory reaction. SBA increases the population of mononuclear cells, the numbers of CD4+/CD8− lymphocytes, the expression of CD11/CD18 surface molecules, and the number of circulating neutrophils and by inhibiting neutrophil migration in rats. An inhibitory effect on neutrophil migration is also observed in the absence of SBA present in the blood circulation (
SBA has a specific binding with the gastrointestinal tract. This specific binding is a precondition for deleterious toxic or side effects (
SBA has been investigated in poultry diets, and it has the ability to bind to the intestinal epithelium and to induce cytotoxic damage on intestinal epithelial cells of broiler chicks (
In other cell lines, SBA induces DNA laddering in a dose-dependent manner and causes DNA fragmentation in HeLa cell lines (
In addition to the direct effects on the structure and biological function of intestinal epithelial cells, SBA can also affect the expression and function of cellular membrane proteins of the gastro-epithelial cells. These effects can be extended to cause cell apoptosis, autophagy and signal transduction.
SBA can use a mechanism to alter cell activity through the mitochondria-mediated pathway. SBA induces apoptosis and autophagic death through ROS generation in HeLa cells (
In addition, SBA induces some structural proteins to alter the cellular biological function. The integrins are involved in SBA-induced IPEC-J2 cellular viability. SBA can indirectly change the expression and function of integrins by binding with α-actinin-2, and then affect the proliferation, cycle and apoptosis in IPEC-J2 cells (
There is limited data available about the similarities among the structure of lectins. However,
Other legume lectins can also cause cell apoptosis and autophagy. Haemagglutinin (PHA-E) of dark red kidney bean can inhibit the proliferation of leukemia L1210 cells. Pea lectin induces apoptosis and cell cycle arrest in colorectal cancer SW480 and SW48 cells (
The pathways of other legume lectins-induced apoptosis, autophagy, or both biological processes, are mainly occurred through the mitochondria-mediated pathway, death receptor pathway, and sugar-binding specificity pathway. Concanavalin A (Con A, a lectin, originated from the jack-bean) induces apoptosis in human melanoma A375 cells through the caspase-dependent pathway and induces autophagy in hepatoma cells through internalization and mitochondrion-mediated pathway (
Plant lectin, a class of highly diverse non-immune origin and carbohydrate-binding proteins, can induce apoptosis, autophagy, or both biological processes. Lectins from
Based on an enormous amount of research, the plant lectins eliminate various types of cancer cells via different major pathways, that including direct ribosome inactivating, endocytosis-dependent mitochondrial dysfunction, sugar-containing receptors binding (
These related studies indicated that legume lectin and plant lectin have similar pathways in inducing apoptosis and autophagy. Such pathways are involving mitochondria-mediated, death receptor, sugar-binding specificity, and direct ribosome inactivating pathway, and other critical impacts such as apoptosis, and autophagy of intestinal cells.
In addition to the pathway described above, to further reveal the signal transduction pathway of apoptosis and autophagy induced by SBA, we need to thoroughly analyze the pathway of cell apoptosis, autophagy, and the relationships between them. Apoptosis and autophagy are important indicators of animal health, since they are programmed cell death processes. Consequently, many studies have been conducted on the signal pathway for apoptosis and autophagy, as well as their mutual interactions.
Apoptosis, is defined as cellular Type-I programmed cell death. It is a conservative and orderly process of cell death. Such an active cell death process involves gene activation, expression and regulation. The character of apoptosis is the condensation of the cytoplasm and nucleus, DNA fragmentation, migration of chromatin to the nuclear periphery, cell contraction, dynamic membrane blebbing, and phagocytosis (
Apoptosis removes aging and abnormal cells in time, and plays a scavenger role. Apoptosis is triggered by three ways, including extrinsic apoptotic pathway, intrinsic apoptosis pathway, and endoplasmic reticulum pathway. The first one is surface death receptors (DR), as called extrinsic apoptosis. In the extrinsic apoptotic pathway, after the binding of cell surface receptors to specific ligands, apoptotic signals are subsequently activated and transmitted, finally enabling the cleavage of caspase-3, 6, and 7. The second way is the mitochondrial release of cytochrome c, called intrinsic apoptosis. In the intrinsic apoptosis pathway, mitochondrial outer membrane permeabilization (MOMP) is induced by the dimerization of pro-apoptotic proteins (Bax and Bak), then cytochrome c is released into the cytosol from the mitochondrial membrane. Subsequently, apoptosome is initiated by the binding of cytochrome c to apoptotic protein activating factor-1, the activates caspase-9, followed by the activation of caspase-3 (
Autophagy, known as Type-II programmed cell death, refers to an evolutionarily conserved, multi-step lysosomal degradation process in which a cell degrades long-lived proteins and damaged organelles (
Autophagy can regulate cell death with dual natures (mild or severe). Mild autophagy can protect cells from harmful conditions to some extent and promote cell survival, while severe or rapid autophagy can induce programmed cell death. Nowadays, the autophagy pathway includes the autophagy-dependent on the membrane target of rapamycin (mTOR) pathway, and the autophagy-independent of the mTOR pathway.
There are PI3K-Akt-mTOR signaling pathway, MAPK signaling pathway and other signaling pathways in the upstream of dependent mTOR signaling molecules, that regulate mTOR molecules and form complex network signaling pathways.
There are positive or negative interconnections between apoptosis and autophagy (
Both apoptosis and autophagy are regulated by some common factors and have some same biological functions. Interestingly, the activity of the apoptosis may be regulated by the autophagic pathway. The main relationships between apoptosis and autophagy may have different possible points.
First, apoptosis and autophagy promote each other. The expression of apoptosis gene and autophagy gene was up-regulated at the same time, and there were many regulatory molecules between apoptosis and autophagy (
Based on the structure and toxic effects of SBA on the cells (apoptosis and autophagy), it can be used in differentiating markers to study cancers and metastatic cell lines, helping in detecting the carbohydrate residues present on the cell surface (
The specific binding of SBA with small intestinal epithelial cells is the prerequisite for its anti-nutrition effect, which will lead to apoptosis and autophagy. We can use these SBA characters to identify the SBA-specific binding proteins on the intestinal epithelial cell membrane. We can constantly uncover the signal transduction vector and possible signal pathway of SBA induced apoptosis and autophagy through
In addition, the development of new technologies related to blocking or reducing the SBA anti-nutritional toxicity needs further investigation.
SBA is a major anti-nutritional factor in soybean, which may induce abnormalities in the biological and metabolic patterns of intestinal cells. It can be inferred that SBA acts in different anti-nutritional mechanisms that including damaging the structure of the intestinal epithelial cells, blocking the cell cycle, promoting apoptosis, autophagy, altering the metabolic and related signal transduction pathways.