Galectin

About: Galectin is a research topic. Over the lifetime, 2076 publications have been published within this topic receiving 103409 citations. The topic is also known as: IPR001079 & Galectin.

The Complex Biological Effects of Pectin: Galectin-3 Targeting as Potential Human Health Improvement?

Abstract: Galectin-3 is the only chimeric representative of the galectin family. Although galectin-3 has ubiquitous regulatory and physiological effects, there is a great number of pathological environments where galectin-3 cooperatively participates. Pectin is composed of different chemical structures, such as homogalacturonans, rhamnogalacturonans, and side chains. The study of pectin’s major structural aspects is fundamental to predicting the impact of pectin on human health, especially regarding distinct molecular modulation. One of the explored pectin’s biological activities is the possible galectin-3 protein regulation. The present review focuses on revealing the structure/function relationship of pectins, their fragments, and their biological effects. The discussion highlighted by this review shows different effects described within in vitro and in vivo experimental models, with interesting and sometimes contradictory results, especially regarding galectin-3 interaction. The review demonstrates that pectins are promissory food-derived molecules for different bioactive functions. However, galectin-3 inhibition by pectin had been stated in literature before, although it is not a fully understood, experimentally convincing, and commonly agreed issue. It is demonstrated that more studies focusing on structural analysis and its relation to the observed beneficial effects, as well as substantial propositions of cause and effect alongside robust data, are needed for different pectin molecules’ interactions with galectin-3.

Galectins and collectinis expression are increased in Haemonchus contortus-infected corriedale sheep

Abstract: Galectins and collectins are proteins classified in the lectin family that have the ability to recognize molecular patterns associated with pathogens. Studies on cattle have demonstrated high expression of these proteins during infection with gastrointestinal nematodes. The aim of this study was to investigate whether the level of Haemonchus contortus infection would alter the expression of galectins (Gal11 and Gal14) and collectins (SPA and CGN) in sheep. Twelve Corriedale sheep exposed to natural infection with nematodes were divided into two groups: group 1 (G1, n = 7) and group 2 (G2, n = 5), with low and high parasite burdens, respectively, based on fecal egg counts and abomasal parasite counts. The fecal egg counts and abomasal parasite counts were significantly different (p < 0.05) between the groups. Galectin and collectin gene expression was observed in all sheep abomasal samples. However, animals with lower infection levels showed lower expression of the genes Gal14, SPA and CGN (p < 0.05). Expression of lectins was associated with the abomasal H. contortus burden, thus suggesting that these proteins may have a role in controlling of this infection.

KIT Mutations Correlate with Higher Galectin Levels and Brain Metastasis in Breast and Non-Small Cell Lung Cancer

Abstract: Simple Summary Galectins are a family of β-galactoside binding proteins whose levels are altered in various stages of different types of cancer. This study provides an analytical comparison of 50 frequently mutated genes in two common cancers and the serum levels of the galectin proteins. The goal is the revelation of potential relationships between the mutation status of these genes and serum levels of galectins. We found that mutations in the KIT gene (which codes for the proto-oncogene c-KIT protein) are associated with increased circulating levels of certain galectins. We also found that patient samples originating from brain tissue have a higher likelihood of having a mutation in the KIT gene. Understanding the relationship between cancer-critical gene mutations and serum galectin levels could provide a feasible and non-invasive avenue to better understand the tumor’s unique genetic profile. Abstract To investigate a potential role for galectins as biomarkers that enable diagnosis or prognostication of breast or non-small cell lung cancer, the serum levels of galectins -1, -3, -7, -8, and -9 of cancer patients determined by ELISA assays were compared to the mutation status of 50 known cancer-critical genes, which were determined using multiplex PCR in tumors of the same patients. Mutations in the KIT proto-oncogene, which codes for the c-Kit protein, a receptor tyrosine kinase, correlated with higher levels of galectins -1, -3, -8, and -9 in breast cancer patients and galectin-1 in non-small cell lung cancer patients. Mutations in the KIT gene were more likely found in brain metastases from both of these primary cancers. The most common KIT mutation in our panel was p.M541L, a missense mutation in the transmembrane domain of the c-Kit protein. These results demonstrate an association between KIT oncogenic signaling and elevated serum galectins in patients with metastatic disease. Changes in protein trafficking and the glycocalyx composition of cancer cells may explain the observed alterations in galectin expression. This study can be useful for the targeted selection of receptor tyrosine kinase and galectin inhibitor anti-cancer treatments.

Synthesis of tricyclic carbohydrate–benzene hybrids as selective inhibitors of galectin-1 and galectin-8 N-terminal domains

Abstract: As the galactoside binding family of galectin proteins is involved in many physiological and pathological processes, the inhibitors of these proteins are considered to be of significant interest in the treatment of diseases such as cancer and fibrosis. Herein, fused tricyclic carbohydrate–benzene hybrid core structures are reported to be the selective inhibitors of galectin-1 and the N-terminal domain of galectin-8 by a competitive fluorescence polarization assay. The key intermediates mono- or diiodo tricyclic carbohydrate–benzene hybrids were synthesized from protected 2-bromo-3-O-propargyl-D-galactose via a domino reaction and subsequently utilized for further derivatization by Stille couplings to achieve derivatives carrying substituents at C10 and/or C11. Several compounds showed affinity for the galectin-1 and galectin-8 N-terminal (8N) domains; however, weak or even no binding was observed for galectin-3. Monosubstituted derivatives at C10 or C11 exhibited better affinity for galectin-8N than di-substituted derivatives at C10 or C11. Especially, a benzyl substituent or p-fluorobenzyl substituent at C11 displayed affinity and selectivity for galectin-1 and galectin-8N over galectin-3. This suggests that tricyclic carbohydrate–benzene hybrids are promising scaffolds for the development of selective galectin-1 and galectin-8N inhibitors.

Galectokines: The Promiscuous Relationship between Galectins and Cytokines

Abstract: Galectins, a family of glycan-binding proteins, are well-known for their role in shaping the immune microenvironment. They can directly affect the activity and survival of different immune cell subtypes. Recent evidence suggests that galectins also indirectly affect the immune response by binding to members of another immunoregulatory protein family, i.e., cytokines. Such galectin-cytokine heterodimers, here referred to as galectokines, add a new layer of complexity to the regulation of immune homeostasis. Here, we summarize the current knowledge with regard to galectokine formation and function. We describe the known and potential mechanisms by which galectokines can help to shape the immune microenvironment. Finally, the outstanding questions and challenges for future research regarding the role of galectokines in immunomodulation are discussed.