Induction of ATP release, PPIX transport, and cholesterol uptake by human red blood cells using a new family of TSPO ligands
Two main isoforms of the Translocator Protein (TSPO) have been identified. TSPO1 is ubiquitous and is mainly present at the outer mitochondrial membrane of most eukaryotic cells, whereas, TSPO2 is specific to the erythroid lineage, located at the plasma membrane, the nucleus, and the endoplasmic ret...
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2018
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_16616596_v19_n10_p_MarginedasFreixa http://hdl.handle.net/20.500.12110/paper_16616596_v19_n10_p_MarginedasFreixa |
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paper:paper_16616596_v19_n10_p_MarginedasFreixa2023-06-08T16:25:42Z Induction of ATP release, PPIX transport, and cholesterol uptake by human red blood cells using a new family of TSPO ligands ATP Erythrocyte Malaria Plasmodium Red blood cell TSPO TSPO2 VDAC ZnPPIX adenine nucleotide translocase adenosine triphosphate antiparasitic agent carrier protein ligand n sec butyl 1 (2 chlorophenyl) n methyl 3 isoquinolinecarboxamide n,n diethyl 2 (2 (furan 2 yl) 5 oxoimidazo[1 c]quinazolin 6(5h) yl)acetamide n,n diethyl 2 (2 (furan 2 yl) 5 oxomidazo[1 c]quinazolin 6(5h) yl)acetamide n,n dipropyl 2 (5 oxo 2 phenylimidazo[1 c]quinazolin 6(5h) yl)acetamide protoporphyrin zinc radioligand reactive oxygen metabolite Ro5 4864 sorbitol SSR 180 575 ubiquitin unclassified drug voltage dependent anion channel 4 aminobutyric acid receptor adenosine triphosphate cholesterol ligand protein binding protoporphyrin reactive oxygen metabolite sorbitol TSPO protein, human antimalarial activity Article binding affinity blood flow cholesterol transport comparative study controlled study erythrocyte erythrocyte function and characteristics erythrocyte lifespan erythrocyte membrane flow cytometry fluorescence growth inhibition hematocrit hemolysis assay human human cell IC50 malaria falciparum normal human parasitemia plasmodium (life cycle stage) protein analysis protein transport supramolecular chemistry tissue oxygenation drug effect hemolysis metabolism Plasmodium falciparum transport at the cellular level Adenosine Triphosphate Biological Transport Cholesterol Erythrocytes Hemolysis Humans Ligands Plasmodium falciparum Protein Binding Protoporphyrins Reactive Oxygen Species Receptors, GABA Sorbitol Two main isoforms of the Translocator Protein (TSPO) have been identified. TSPO1 is ubiquitous and is mainly present at the outer mitochondrial membrane of most eukaryotic cells, whereas, TSPO2 is specific to the erythroid lineage, located at the plasma membrane, the nucleus, and the endoplasmic reticulum. The design of specific tools is necessary to determine the molecular associations and functions of TSPO, which remain controversial nowadays. We recently demonstrated that TSPO2 is involved in a supramolecular complex of the erythrocyte membrane, where micromolar doses of the classical TSPO ligands induce ATP release and zinc protoporphyrin (ZnPPIX) transport. In this work, three newly-designed ligands (NCS1016, NCS1018, and NCS1026) were assessed for their ability to modulate the functions of various erythrocyte’s and compare them to the TSPO classical ligands. The three new ligands were effective in reducing intraerythrocytic Plasmodium growth, without compromising erythrocyte survival. While NCS1016 and NCS1018 were the most effective ligands in delaying sorbitol-induced hemolysis, NCS1016 induced the highest uptake of ZnPPIX and NCS1026 was the only ligand inhibiting the cholesterol uptake. Differential effects of ligands are probably due, not only, to ligand features, but also to the dynamic interaction of TSPO with various partners at the cell membrane. Further studies are necessary to fully understand the mechanisms of the TSPO’s complex activation. © 2018 by the authors. Licensee MDPI, Basel, Switzerland. 2018 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_16616596_v19_n10_p_MarginedasFreixa http://hdl.handle.net/20.500.12110/paper_16616596_v19_n10_p_MarginedasFreixa |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
ATP Erythrocyte Malaria Plasmodium Red blood cell TSPO TSPO2 VDAC ZnPPIX adenine nucleotide translocase adenosine triphosphate antiparasitic agent carrier protein ligand n sec butyl 1 (2 chlorophenyl) n methyl 3 isoquinolinecarboxamide n,n diethyl 2 (2 (furan 2 yl) 5 oxoimidazo[1 c]quinazolin 6(5h) yl)acetamide n,n diethyl 2 (2 (furan 2 yl) 5 oxomidazo[1 c]quinazolin 6(5h) yl)acetamide n,n dipropyl 2 (5 oxo 2 phenylimidazo[1 c]quinazolin 6(5h) yl)acetamide protoporphyrin zinc radioligand reactive oxygen metabolite Ro5 4864 sorbitol SSR 180 575 ubiquitin unclassified drug voltage dependent anion channel 4 aminobutyric acid receptor adenosine triphosphate cholesterol ligand protein binding protoporphyrin reactive oxygen metabolite sorbitol TSPO protein, human antimalarial activity Article binding affinity blood flow cholesterol transport comparative study controlled study erythrocyte erythrocyte function and characteristics erythrocyte lifespan erythrocyte membrane flow cytometry fluorescence growth inhibition hematocrit hemolysis assay human human cell IC50 malaria falciparum normal human parasitemia plasmodium (life cycle stage) protein analysis protein transport supramolecular chemistry tissue oxygenation drug effect hemolysis metabolism Plasmodium falciparum transport at the cellular level Adenosine Triphosphate Biological Transport Cholesterol Erythrocytes Hemolysis Humans Ligands Plasmodium falciparum Protein Binding Protoporphyrins Reactive Oxygen Species Receptors, GABA Sorbitol |
| spellingShingle |
ATP Erythrocyte Malaria Plasmodium Red blood cell TSPO TSPO2 VDAC ZnPPIX adenine nucleotide translocase adenosine triphosphate antiparasitic agent carrier protein ligand n sec butyl 1 (2 chlorophenyl) n methyl 3 isoquinolinecarboxamide n,n diethyl 2 (2 (furan 2 yl) 5 oxoimidazo[1 c]quinazolin 6(5h) yl)acetamide n,n diethyl 2 (2 (furan 2 yl) 5 oxomidazo[1 c]quinazolin 6(5h) yl)acetamide n,n dipropyl 2 (5 oxo 2 phenylimidazo[1 c]quinazolin 6(5h) yl)acetamide protoporphyrin zinc radioligand reactive oxygen metabolite Ro5 4864 sorbitol SSR 180 575 ubiquitin unclassified drug voltage dependent anion channel 4 aminobutyric acid receptor adenosine triphosphate cholesterol ligand protein binding protoporphyrin reactive oxygen metabolite sorbitol TSPO protein, human antimalarial activity Article binding affinity blood flow cholesterol transport comparative study controlled study erythrocyte erythrocyte function and characteristics erythrocyte lifespan erythrocyte membrane flow cytometry fluorescence growth inhibition hematocrit hemolysis assay human human cell IC50 malaria falciparum normal human parasitemia plasmodium (life cycle stage) protein analysis protein transport supramolecular chemistry tissue oxygenation drug effect hemolysis metabolism Plasmodium falciparum transport at the cellular level Adenosine Triphosphate Biological Transport Cholesterol Erythrocytes Hemolysis Humans Ligands Plasmodium falciparum Protein Binding Protoporphyrins Reactive Oxygen Species Receptors, GABA Sorbitol Induction of ATP release, PPIX transport, and cholesterol uptake by human red blood cells using a new family of TSPO ligands |
| topic_facet |
ATP Erythrocyte Malaria Plasmodium Red blood cell TSPO TSPO2 VDAC ZnPPIX adenine nucleotide translocase adenosine triphosphate antiparasitic agent carrier protein ligand n sec butyl 1 (2 chlorophenyl) n methyl 3 isoquinolinecarboxamide n,n diethyl 2 (2 (furan 2 yl) 5 oxoimidazo[1 c]quinazolin 6(5h) yl)acetamide n,n diethyl 2 (2 (furan 2 yl) 5 oxomidazo[1 c]quinazolin 6(5h) yl)acetamide n,n dipropyl 2 (5 oxo 2 phenylimidazo[1 c]quinazolin 6(5h) yl)acetamide protoporphyrin zinc radioligand reactive oxygen metabolite Ro5 4864 sorbitol SSR 180 575 ubiquitin unclassified drug voltage dependent anion channel 4 aminobutyric acid receptor adenosine triphosphate cholesterol ligand protein binding protoporphyrin reactive oxygen metabolite sorbitol TSPO protein, human antimalarial activity Article binding affinity blood flow cholesterol transport comparative study controlled study erythrocyte erythrocyte function and characteristics erythrocyte lifespan erythrocyte membrane flow cytometry fluorescence growth inhibition hematocrit hemolysis assay human human cell IC50 malaria falciparum normal human parasitemia plasmodium (life cycle stage) protein analysis protein transport supramolecular chemistry tissue oxygenation drug effect hemolysis metabolism Plasmodium falciparum transport at the cellular level Adenosine Triphosphate Biological Transport Cholesterol Erythrocytes Hemolysis Humans Ligands Plasmodium falciparum Protein Binding Protoporphyrins Reactive Oxygen Species Receptors, GABA Sorbitol |
| description |
Two main isoforms of the Translocator Protein (TSPO) have been identified. TSPO1 is ubiquitous and is mainly present at the outer mitochondrial membrane of most eukaryotic cells, whereas, TSPO2 is specific to the erythroid lineage, located at the plasma membrane, the nucleus, and the endoplasmic reticulum. The design of specific tools is necessary to determine the molecular associations and functions of TSPO, which remain controversial nowadays. We recently demonstrated that TSPO2 is involved in a supramolecular complex of the erythrocyte membrane, where micromolar doses of the classical TSPO ligands induce ATP release and zinc protoporphyrin (ZnPPIX) transport. In this work, three newly-designed ligands (NCS1016, NCS1018, and NCS1026) were assessed for their ability to modulate the functions of various erythrocyte’s and compare them to the TSPO classical ligands. The three new ligands were effective in reducing intraerythrocytic Plasmodium growth, without compromising erythrocyte survival. While NCS1016 and NCS1018 were the most effective ligands in delaying sorbitol-induced hemolysis, NCS1016 induced the highest uptake of ZnPPIX and NCS1026 was the only ligand inhibiting the cholesterol uptake. Differential effects of ligands are probably due, not only, to ligand features, but also to the dynamic interaction of TSPO with various partners at the cell membrane. Further studies are necessary to fully understand the mechanisms of the TSPO’s complex activation. © 2018 by the authors. Licensee MDPI, Basel, Switzerland. |
| title |
Induction of ATP release, PPIX transport, and cholesterol uptake by human red blood cells using a new family of TSPO ligands |
| title_short |
Induction of ATP release, PPIX transport, and cholesterol uptake by human red blood cells using a new family of TSPO ligands |
| title_full |
Induction of ATP release, PPIX transport, and cholesterol uptake by human red blood cells using a new family of TSPO ligands |
| title_fullStr |
Induction of ATP release, PPIX transport, and cholesterol uptake by human red blood cells using a new family of TSPO ligands |
| title_full_unstemmed |
Induction of ATP release, PPIX transport, and cholesterol uptake by human red blood cells using a new family of TSPO ligands |
| title_sort |
induction of atp release, ppix transport, and cholesterol uptake by human red blood cells using a new family of tspo ligands |
| publishDate |
2018 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_16616596_v19_n10_p_MarginedasFreixa http://hdl.handle.net/20.500.12110/paper_16616596_v19_n10_p_MarginedasFreixa |
| _version_ |
1768542615964221440 |