Antioxidative CXXC Peptide Motif From Mesencephalic Astrocyte-Derived Neurotrophic Factor Antagonizes Programmed Cell Death
Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a potent survival-promoting protein with neurorestorative effect for neurodegenerative diseases. Its mechanism of action, albeit poorly known, depends strongly on the CXXC motif (CKGC). Here we studied the survival-promoting properties of...
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Frontiers Media S.A.
2018-09-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2018.00106/full |
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| author | Valentina Božok Li-ying Yu Jaan Palgi Urmas Arumäe Urmas Arumäe |
| author_facet | Valentina Božok Li-ying Yu Jaan Palgi Urmas Arumäe Urmas Arumäe |
| author_sort | Valentina Božok |
| collection | DOAJ |
| description | Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a potent survival-promoting protein with neurorestorative effect for neurodegenerative diseases. Its mechanism of action, albeit poorly known, depends strongly on the CXXC motif (CKGC). Here we studied the survival-promoting properties of the CKGC tetrapeptide from MANF. In the Jurkat T lymphocytic cell line, CKGC potently inhibits death receptor Fas-induced apoptosis and mildly counteracts mitochondrial apoptosis and necroptosis. The peptide with serines instead of cysteines (SKGS) has no survival-promoting activity. The cytoprotective efficiency of the peptide against Fas-induced apoptosis is significantly improved by reduction of its cysteines by dithiotreitol, suggesting that it protects the cells via cysteine thiol groups, partially as an antioxidant. CKGC neutralizes the reactive oxygen species, maintains the mitochondrial membrane potential and prevents activation of the effector caspases in the Jurkat cells with activated Fas. The peptide does not require intracellular administration, as it is endocytosed and resides mainly in the Golgi. Finally, the peptide also potently promotes survival of cultured primary dopaminergic neurons. |
| first_indexed | 2024-04-12T02:32:46Z |
| format | Article |
| id | doaj.art-0cde5fcfcfe844e38ac0b2c8bd164c66 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-12T02:32:46Z |
| publishDate | 2018-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-0cde5fcfcfe844e38ac0b2c8bd164c662022-12-22T03:51:43ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2018-09-01610.3389/fcell.2018.00106390059Antioxidative CXXC Peptide Motif From Mesencephalic Astrocyte-Derived Neurotrophic Factor Antagonizes Programmed Cell DeathValentina Božok0Li-ying Yu1Jaan Palgi2Urmas Arumäe3Urmas Arumäe4Division of Gene Technology, Department of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, EstoniaInstitute of Biotechnology, University of Helsinki, Helsinki, FinlandDivision of Gene Technology, Department of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, EstoniaDivision of Gene Technology, Department of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, EstoniaInstitute of Biotechnology, University of Helsinki, Helsinki, FinlandMesencephalic astrocyte-derived neurotrophic factor (MANF) is a potent survival-promoting protein with neurorestorative effect for neurodegenerative diseases. Its mechanism of action, albeit poorly known, depends strongly on the CXXC motif (CKGC). Here we studied the survival-promoting properties of the CKGC tetrapeptide from MANF. In the Jurkat T lymphocytic cell line, CKGC potently inhibits death receptor Fas-induced apoptosis and mildly counteracts mitochondrial apoptosis and necroptosis. The peptide with serines instead of cysteines (SKGS) has no survival-promoting activity. The cytoprotective efficiency of the peptide against Fas-induced apoptosis is significantly improved by reduction of its cysteines by dithiotreitol, suggesting that it protects the cells via cysteine thiol groups, partially as an antioxidant. CKGC neutralizes the reactive oxygen species, maintains the mitochondrial membrane potential and prevents activation of the effector caspases in the Jurkat cells with activated Fas. The peptide does not require intracellular administration, as it is endocytosed and resides mainly in the Golgi. Finally, the peptide also potently promotes survival of cultured primary dopaminergic neurons.https://www.frontiersin.org/article/10.3389/fcell.2018.00106/fullCXXC motifapoptosisFasreactive oxygen speciesMANFdopaminergic neurons |
| spellingShingle | Valentina Božok Li-ying Yu Jaan Palgi Urmas Arumäe Urmas Arumäe Antioxidative CXXC Peptide Motif From Mesencephalic Astrocyte-Derived Neurotrophic Factor Antagonizes Programmed Cell Death Frontiers in Cell and Developmental Biology CXXC motif apoptosis Fas reactive oxygen species MANF dopaminergic neurons |
| title | Antioxidative CXXC Peptide Motif From Mesencephalic Astrocyte-Derived Neurotrophic Factor Antagonizes Programmed Cell Death |
| title_full | Antioxidative CXXC Peptide Motif From Mesencephalic Astrocyte-Derived Neurotrophic Factor Antagonizes Programmed Cell Death |
| title_fullStr | Antioxidative CXXC Peptide Motif From Mesencephalic Astrocyte-Derived Neurotrophic Factor Antagonizes Programmed Cell Death |
| title_full_unstemmed | Antioxidative CXXC Peptide Motif From Mesencephalic Astrocyte-Derived Neurotrophic Factor Antagonizes Programmed Cell Death |
| title_short | Antioxidative CXXC Peptide Motif From Mesencephalic Astrocyte-Derived Neurotrophic Factor Antagonizes Programmed Cell Death |
| title_sort | antioxidative cxxc peptide motif from mesencephalic astrocyte derived neurotrophic factor antagonizes programmed cell death |
| topic | CXXC motif apoptosis Fas reactive oxygen species MANF dopaminergic neurons |
| url | https://www.frontiersin.org/article/10.3389/fcell.2018.00106/full |
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