Is related the hematopoietic stem cells differentiation in the Nile tilapia with GABA exposure?

Vega-López, Armando; Pagadala, Nataraj Sekhar; López-Tapia, Brenda P.; Madera-Sandoval, Ruth L.; Rosales-Cruz, Érika; Nájera-Martínez, Minerva; Reyes‐Maldonado, Elba

doi:10.1016/j.fsi.2019.08.032

Cited by 7 publications

(3 citation statements)

References 95 publications

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“…They displayed markers of immaturity/activation, even though, in the higher dose of NCTD (3.0 mg/kg), the activation of NK cells was also related to these markers of immaturity, as observed in the control group. This statistical relationship again corroborates the importance of c-kit as a transcription factor involved in hematopoietic development and increased cytotoxic potential [28,30,[40][41][42][43][44]. These results contrast those found in vitro, where NCTD was shown to suppress lymphocyte activation [19], which is very likely to occur in vitro since NCTD is a potent inhibitor of protein phosphatases 1, 2A, 2B, and 5 [45].…”

Section: Discussionsupporting

confidence: 70%

“…In addition, this protein synergizes with hematopoietic growth factors such as erythropoietin, granulocyte colony-stimulating factor (G-CSF), and granulocyte/macrophage-colony-stimulating factor (GM-CSF) [29]. The helix-loop-helix heterodimer (SCL, most probably coupled with bHLH E12/E47) DNA-binding domain acts as a transcription factor [28,30]. In the specific case of NK cells in a mouse-melanoma model, this binding promotes the survival of peripheral CD16 + CD56+c-kit+Sca-1+ cells.…”

Section: Discussionmentioning

confidence: 99%

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Tumor-Infiltrating iNKT Cells Activated through c-Kit/Sca-1 Are Induced by Pentoxifylline, Norcantharidin, and Their Mixtures for Killing Murine Melanoma Cells

Correa-Lara,

Lara-Vega,

Nájera-Martínez

et al. 2023

Pharmaceuticals

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The involvement of NK and other cytotoxic cells is considered the first defense line against cancer. However, a significant lack of information prevails on the possible roles played by factors considered characteristic of primitive cells, such as c-kit and Sca-1, in activating these cells, particularly in melanoma models subjected to treatments with substances under investigation, such as the case of norcantharidin. In this study, B16F1 murine melanoma cells were used to induce tumors in DBA/2 mice, estimating the proportions of NK and iNKT cells; the presence of activation (CD107a+) and primitive/activation (c-kit+/Lya6A+) markers and some tumor parameters, such as the presence of mitotic bodies, nuclear factor area, NK and iNKT cell infiltration in the tumor, infiltrated tumor area, and infiltrating lymphocyte count at 10x and 40x in specimens treated with pentoxifylline, norcantharidin, and the combination of both drugs. Possible correlations were estimated with Pearson’s correlation analysis. It should be noted that, despite having demonstrated multiple correlations, immaturity/activation markers were related to these cells’ activation. At the tumor site, iNKT cells are the ones that exert the cytotoxic potential on tumor cells, but they are confined to specific sites in the tumor. Due to the higher number of interactions of natural killer cells with tumor cells, it is concluded that the most effective treatment was PTX at 60 mg/kg + NCTD at 0.75 mg/kg.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Tumor-Infiltrating iNKT Cells Activated through c-Kit/Sca-1 Are Induced by Pentoxifylline, Norcantharidin, and Their Mixtures for Killing Murine Melanoma Cells

Correa-Lara,

Lara-Vega,

Nájera-Martínez

et al. 2023

Pharmaceuticals

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“…Studies in Drosophila and bony fish showed that GABA signaling regulates hematopoietic progenitors, suggesting an ancient and deeply conserved role in hematopoiesis. 46,47 Interestingly, genome-wide association studies have identified a rare variant in the GABBR1 locus that produces a change in WBC and lymphocyte counts. 48,49 Although further mechanistic investigation is required to fully determine the role of neurotransmitter signaling in BM HSPC populations, our ex vivo findings suggest a potential direct translational application for activation of GABA signaling in enhancing engraftment during clinical transplant.…”

Section: Discussionmentioning

confidence: 99%

The neurotransmitter receptor Gabbr1 regulates proliferation and function of hematopoietic stem and progenitor cells

Shao

Elujoba-Bridenstine

Zink

et al. 2021

Blood

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Hematopoietic and nervous systems are linked via innervation of bone marrow (BM) niche cells. Hematopoietic stem/progenitor cells (HSPCs) express neurotransmitter receptors, such as the g-aminobutyric acid (GABA) type B receptor subunit 1 (GABBR1), suggesting that HSPCs could be directly regulated by neurotransmitters like GABA that directly bind to GABBR1. We performed imaging mass spectrometry (IMS) and found that endogenous GABA molecule is regionally localized and concentrated near the endosteum of the BM niche. To better understand the role of GABBR1 in regulating HSPCs, we generated a constitutive Gabbr1 knockout mouse model. Analysis revealed that HSPC numbers were significantly reduced in the BM compared to wild-type littermates. Moreover, Gabbr1 null hematopoietic stem cells (HSCs) had diminished capacity to reconstitute irradiated recipients in a competitive transplantation model. Gabbr1 null HSPCs were less proliferative under steady-state conditions and upon stress. Colony assays demonstrated that almost all Gabbr1 null HSPCs were in a slow or non-cycling state. In vitro differentiation of Gabbr1 null HSPCs in co-cultures, produced fewer overall cell numbers with significant defects in differentiation and expansion of the B cell lineage. To determine if GABBR1 agonist could stimulate human umbilical cord blood (UCB) HSPCs, we performed brief ex vivo treatment prior to transplant into immunodeficient mice, with significant increases in long-term engraftment of HSPCs compared to GABBR1 antagonist or vehicle treatments. Our results indicate a direct role for GABBR1 in HSPC proliferation, and identify a potential target to improve HSPC engraftment in clinical transplantation.

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Disruption of Neurotransmission, Membrane Potential, and Mitochondrial Calcium in the Brain and Spinal Cord of Nile Tilapia Elicited by Microcystis aeruginosa Extract: an Uncommon Consequence of the Eutrophication Process

Nájera-Martínez

Landon-Hernández

Romero-López

et al. 2021

Water Air Soil Pollut

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Microcystins (MCs) are produced during the growth and proliferation of some species of cyanobacteria, mainly Microcystis aeruginosa, which has massive growth in eutrophic water bodies. Microcystins are highly toxic Microcystisderived metabolites that exert its main effect in the liver through the inhibition of protein phosphatase (PP1 and PP2A).However, other damages in sh species are less documented and could be unexpected. The aim of the current study was to evaluate the effects of Microcystis aeruginosa extract (MaE) into the central nervous system (CNS) of the Nile tilapia. The MaE was normalized by MCs content (MC-LR). We include a positive control for protein phosphatase inhibition, norcantharidin intraperitoneally dosed at sublethal levels. On the eighth day, measurement of neurotransmission biomarkers (AChE, BChE, CbE and GABA) were measured, as well as levels of mitochondrial calcium, and the mitochondrial membrane potential by ow cytometry in the brain and spinal cord were assessed, in addition to the PP1/PP2A activity in the liver. The MCs elicited mortality at 5 µg/L. The positive control and MCs at sublethal levels inhibited the PP1/PP2A activity in the liver and induced alterations in the neurotoxicity biomarkers evaluated in the CNS.This response is probably due to the disruption of transport ions, dependent and independent of ATP because of alterations in the mitochondrial membrane potential and mitochondrial calcium. The ndings of this study suggest that pollutants capable of inducing cyanobacterial blooms are able, in an indirect way, to exert neurotoxic effects in sh species through MC levels.

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Is related the hematopoietic stem cells differentiation in the Nile tilapia with GABA exposure?

Cited by 7 publications

References 95 publications

Tumor-Infiltrating iNKT Cells Activated through c-Kit/Sca-1 Are Induced by Pentoxifylline, Norcantharidin, and Their Mixtures for Killing Murine Melanoma Cells

Tumor-Infiltrating iNKT Cells Activated through c-Kit/Sca-1 Are Induced by Pentoxifylline, Norcantharidin, and Their Mixtures for Killing Murine Melanoma Cells

The neurotransmitter receptor Gabbr1 regulates proliferation and function of hematopoietic stem and progenitor cells

Disruption of Neurotransmission, Membrane Potential, and Mitochondrial Calcium in the Brain and Spinal Cord of Nile Tilapia Elicited by Microcystis aeruginosa Extract: an Uncommon Consequence of the Eutrophication Process

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