Galectin-12 inhibits granulocytic differentiation of human NB4 promyelocytic leukemia cells while promoting lipogenesis (original) (raw)
Related papers
Galectin-12 in Cellular Differentiation, Apoptosis and Polarization
International Journal of Molecular Sciences
Galectin-12 is a member of a family of mammalian lectins characterized by their affinity for β-galactosides and consensus amino acid sequences. The protein structure consists of a single polypeptide chain containing two carbohydrate-recognition domains joined by a linker region. Galectin-12 is predominantly expressed in adipose tissue, but is also detected in macrophages and other leukocytes. Downregulation of galectin-12 in mouse 3T3-L1 cells impairs their differentiation into adipocytes. Conversely, overexpression of galectin-12 in vitro induces cell cycle arrest in G1 and apoptosis. Upregulation of galectin-12 and initiation of G1 cell cycle arrest are associated with driving pre-adipocytes toward terminal differentiation. Galectin-12 deficiency increases insulin sensitivity and glucose tolerance in obese animals. Galectin-12 inhibits macrophage polarization to the M2 population, enhancing inflammation and decreasing insulin sensitivity in adipocytes. Galectin-12 also affects myeloid differentiation, which is associated with chemotherapy resistance. In addition to highlighting the above-mentioned aspects, this review also discusses the potential clinical applications of modulating the function of galectin-12.
Galectin-12 is required for adipogenic signaling and adipocyte differentiation
Journal of Biological Chemistry, 2004
Galectin-12 is a member of the galectin family consisting of -galactoside-binding proteins with conserved carbohydrate recognition domains. This protein is preferentially expressed in peripheral blood leukocytes and adipocytes. We previously showed that galectin-12 is induced by cell cycle block at the G 1 phase and causes G 1 arrest when overexpressed (
International Journal of Pharmacy and Pharmaceutical Sciences, 2016
Objective: The rationale of the present research work was to get insights of galectin-3 function in modulating inflammation in macrophages and adipocytes culture systems. Methods: Recombinant galectin-3 was prepared, and anti-inflammatory effect of galectin-3 was studied in 3T3-L adipocytes and RAW264.7 macrophages stimulated with lipopolysaccharide followed by western blot analysis. Furthermore, we determined the galectin-3 effect on LPS-mediated ROS and NO generation in RAW macrophage cells by using DHE and mitochondrial membrane potential was measured by JC-1 respectively. Results: Galectin-3 negatively regulates the exaggerated inflammatory response in the presence of lipopolysaccharide, by lowering cytokines in adipocytes and macrophages. Reduced oxidative stress was evident as the production of ROS and NO was diminished to a great extent by galectin-3 in lipopolysaccharide-treated macrophages. This was also confirmed by the ability of galectin-3 in the maintenance of mitochondrial membrane potential against lipopolysaccharide-induced massive membrane depolarization by galectin-3. Conclusion: Based on the results obtained, it is rational to mention that galectin-3 exhibits significant anti-inflammatory and anti-oxidative effects in adipocyte and macrophage culture systems, when exposed to lipopolysaccharide.
Adipocyte, 2012
Galectin-12, a member of the galectin family of animal lectins, is preferentially expressed in adipocytes. We recently reported that this galectin is localized on lipid droplets, specialized organelles for fat storage. Galectin-12 regulates lipid degradation (lipolysis) by modulating lipolytic protein kinase A (PKA) signaling. Mice deficient in galectin-12 exhibit enhanced adipocyte lipolysis, increased mitochondria respiration, reduced adiposity and ameliorated insulin resistance associated with weight gain. The results suggest that galectin-12 may be a useful target for treatment of obesity-related metabolic conditions, such as insulin resistance, metabolic syndrome, and type 2 diabetes. Most previously described galectins largely reside in the cytosol, although they can also be induced to become associated with membrane-containing structures. Along with an in-depth characterization of galectin-12, this mini-review comments on this first report of a galectin normally localized spe...
Expression profiling of cancer-related galectins in acute myeloid leukemia
Tumor Biology, 2015
Acute myeloid leukemia (AML) is the most common type of leukemia in adults with the lowest survival rate of all the leukemias. It is a heterogeneous disease in which a variety of cytogenetic and molecular alterations have been identified. Some galectins were previously reported to have important roles in cancer-like neoplastic transformation, tumor cell survival, angiogenesis, and tumor metastasis. Previous studies have showed that some galectin family members play a role in various types of leukemia. The present study aims at evaluating and clarifying the diagnostic and prognostic value of the expression of cancer-related galectins in relation to the clinicopathological characters of AML patients. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect expression profile of eight galectin family members (galectin-1,-2,-3,-4,-8,-9,-12, and-13) in 53 newly diagnosed de novo AML patients. The samples were collected from the inpatient clinic at National Cancer Institute (NCI), Cairo University (CU), diagnosed between July 2012 and May 2013. Our results show that patients with lower LGALS12 gene expression have a lower overall survival than those with higher expression (P value <0.026). Moreover, a statistically significant association between the LGALS4 gene expression and patient age is found. Hence, the higher expression of LGALS4 gene is associated with younger age (adjusted P value <0.001). In conclusion, galectin-12 may be a potential prognostic marker for AML.
Biphasic Effect of Recombinant Galectin‐1 on the Growth and Death of Early Hematopoietic Cells
STEM CELLS, 2005
Galectin-1 is a member of the family of β-galactoside binding animal lectins, galectins. Its presence in the bone marrow has been detected; however, its role in the regulation of hematopoiesis is unknown. In the present study, we have evaluated the effect of recombinant human galectin-1 on the proliferation and survival of murine and human hematopoietic stem and progenitor cells. We show that low amount of galectin-1 (10 ng/ml) increases the formation of granulocyte-macrophage and erythroid colonies and the frequencies of day-7 cobblestone area-forming cells on a lactose-inhibit-able fashion. In contrast, high amount of galectin-1 (10 μg/ml) dramatically reduces the growth of the committed blood-forming progenitor cells as well as the much younger, lineage-negative hematopoietic cells (day-28 to-35 cobblestone area-forming cells). This inhibition is not blocked by lactose and, therefore, is largely independent of the β-galactoside-binding site of the lectin. Furthermore, assays to detect apoptosis render it likely that the high amount of galectin-1 acts as a classical proapoptotic factor for the premature hematopoietic cells.
Expression of galectin-3 modulates T-cell growth and apoptosis
Proceedings of the National Academy of Sciences, 1996
Galectin-3 is a member of a large family of ,B-galactoside-binding animal lectins. It has been shown that the expression of galectin-3 is upregulated in proliferating cells, suggesting a possible role for this lectin in regulation of cell growth. Previously, we have shown that T cells infected with human T-cell leukemia virus type I express high levels of galectin-3, in contrast to uninfected cells, which do not express detectable amounts of this protein. In this study, we examined growth properties of human leukemia T cells transfected with galectin-3 cDNA, and thus constitutively overexpressing this lectin. Transfectants expressing galectin-3 displayed higher growth rates than control transfectants, which do not express this lectin. Furthermore, galectin-3 expression in these cells confers resistance to apoptosis induced by anti-Fas antibody and staurosporine. Galectin-3 was found to have significant sequence similarity with Bcl-2, a well-characterized suppressor of apoptosis. In particular, the lectin contains the NWGR motif that is highly conserved among members of the Bcl-2 family and shown to be critical for the apoptosis-suppressing activity. We further demonstrated that galectin-3 interacts with Bcl-2 in a lactose-inhibitable manner. We conclude that galectin-3 is a regulator of cell growth and apoptosis and it may function through a cell death inhibition pathway that involves Bcl-2.