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Galectin-1: biphasic growth regulation of Leydig tumor cells
Verónica A Biron1, M Mercedes Iglesias, María F Troncoso
1Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón II, Ciudad Universitaria, (1428) Buenos Aires, Argentina.
Abstract:
Galectin-1 (Gal-1) is a widely expressed beta-galactoside-binding protein that exerts pleiotropic biological functions. To gain insight into the potential role of Gal-1 as a novel modulator of Leydig cells, we investigated its effect on the growth and death of MA-10 tumor Leydig cells. In this study, we identified cytoplasmic Gal-1 expression in these tumor cells by cytofluorometry. DNA fragmentation, caspase-3, -8, and -9 activation, loss of mitochondrial membrane potential (DeltaPsim), cytochrome c (Cyt c) release, and FasL expression suggested that relatively high concentrations of exogenously added recombinant Gal-1 (rGal-1) induced apoptosis by the mitochondrial and death receptor pathways. These pathways were independently activated, as the presence of the inhibitor of caspase-8 or -9 only partially prevented Gal-1-effect. On the contrary, low concentrations of Gal-1 significantly promoted cell proliferation, without inducing cell death. Importantly, the presence of the disaccharide lactose prevented Gal-1 effects, suggesting the involvement of the carbohydrate recognition domain (CRD). This study provides strong evidence that Gal-1 is a novel biphasic regulator of Leydig tumor cell number, suggesting a novel role for Gal-1 in the reproductive physiopathology.
Insights
Galectin-1 (Gal-1) has a dual role in Leydig tumor cells. Low concentrations promote proliferation, while high concentrations induce apoptosis via mitochondrial and death receptor pathways, suggesting a novel role in reproductive health.
Area of Science:
- Endocrinology
- Cell Biology
- Reproductive Biology
Background:
- Galectin-1 (Gal-1) is a beta-galactoside-binding protein with diverse biological roles.
- Leydig cells are crucial for testosterone production and reproductive function.
- The role of Gal-1 in Leydig cell physiology is not well understood.
Purpose of the Study:
- To investigate the effect of Gal-1 on the growth and death of MA-10 tumor Leydig cells.
- To elucidate the mechanisms by which Gal-1 modulates Leydig cell proliferation and apoptosis.
- To explore the potential role of Gal-1 in reproductive physiopathology.
Main Methods:
- Cytofluorometry to detect cytoplasmic Gal-1 expression.
- Assays for DNA fragmentation, caspase activation (caspase-3, -8, -9), mitochondrial membrane potential (DeltaPsim), and cytochrome c (Cyt c) release.
- Assessment of FasL expression.
- Treatment with recombinant Gal-1 (rGal-1) at varying concentrations and with lactose.
Main Results:
- Cytoplasmic Gal-1 was identified in MA-10 tumor Leydig cells.
- High concentrations of rGal-1 induced apoptosis through both mitochondrial and death receptor pathways, evidenced by DNA fragmentation, caspase activation, loss of DeltaPsim, Cyt c release, and FasL expression.
- These apoptotic pathways were independently activated.
- Low concentrations of Gal-1 significantly promoted cell proliferation without inducing cell death.
- Lactose inhibited Gal-1 effects, indicating the involvement of its carbohydrate recognition domain (CRD).
Conclusions:
- Galectin-1 acts as a novel biphasic regulator of Leydig tumor cell number.
- Gal-1 can promote Leydig cell proliferation at low concentrations and induce apoptosis at high concentrations.
- The findings suggest a novel role for Gal-1 in reproductive physiopathology.
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