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| Main Authors: | , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Journal of natural products
2026
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/42080225/ |
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| _version_ | 1868266053572755457 |
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| author | Bonar, Sophia E Mattos, Daphne R Yu, Xinhui Neuhaus, George F Youssef, Diaa T A Shaala, Lamiaa A Gerwick, William H McPhail, Kerry L Ishmael, Jane E |
| author_facet | Bonar, Sophia E Mattos, Daphne R Yu, Xinhui Neuhaus, George F Youssef, Diaa T A Shaala, Lamiaa A Gerwick, William H McPhail, Kerry L Ishmael, Jane E Bonar, Sophia E Mattos, Daphne R Yu, Xinhui Neuhaus, George F Youssef, Diaa T A Shaala, Lamiaa A Gerwick, William H McPhail, Kerry L Ishmael, Jane E |
| collection | PubMed - marine biology |
| contents | Identification of Hoiamide A as an Inducer of Oxidative and Endoplasmic Reticulum Secretory Pathway Stress. Bonar, Sophia E Mattos, Daphne R Yu, Xinhui Neuhaus, George F Youssef, Diaa T A Shaala, Lamiaa A Gerwick, William H McPhail, Kerry L Ishmael, Jane E Humans Endoplasmic Reticulum Stress Oxidative Stress Endoplasmic Reticulum Depsipeptides Molecular Structure Secretory Pathway Superoxide Dismutase-1 Cell Line, Tumor Transcription Factor CHOP Cyanobacteria The endoplasmic reticulum (ER) to Golgi secretory compartment of eukaryotic cells is highly sensitive to changes in intracellular homeostasis. Using a primary screening assay that monitors the function of this pathway, we prioritized a cyanobacterial extract from the Red Sea that decreased secretion of a bioluminescent reporter, luciferase (GLuc), in living cells. A comparison of LCMS2 data against the GNPS database revealed a match for macrocyclic depsipeptide hoiamide A (). Biological testing confirmed the ability of to induce a mixed, non-lethal stress response in human U87-MG glioblastoma cells; analysis of stress markers by qRT-PCR revealed early upregulation of superoxide dismutase 1 (SOD1) and C/EBP-homologous protein (CHOP) relative to the control. Co-treatment of cells with (100 nM to 3 μM) and antioxidant -acetylcysteine afforded full protection from -induced decreases in GLuc secretion. We report that terminally differentiated human SH-SY5Y neuroblastoma cells, with a neuron-like phenotype, are highly sensitive to nanomolar concentrations of , whereas undifferentiated cells remained viable at 3 μM. These results expand the known biology of hoiamides and suggest that neurotoxic potential of is likely due to an inherent failure of neurons to adapt to the loss of redox homeostasis and sustained ER stress. |
| format | Artículo científico |
| id | pubmed_42080225 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | Journal of natural products |
| record_format | pubmed |
| spellingShingle | Identification of Hoiamide A as an Inducer of Oxidative and Endoplasmic Reticulum Secretory Pathway Stress. Bonar, Sophia E Mattos, Daphne R Yu, Xinhui Neuhaus, George F Youssef, Diaa T A Shaala, Lamiaa A Gerwick, William H McPhail, Kerry L Ishmael, Jane E Humans Endoplasmic Reticulum Stress Oxidative Stress Endoplasmic Reticulum Depsipeptides Molecular Structure Secretory Pathway Superoxide Dismutase-1 Cell Line, Tumor Transcription Factor CHOP Cyanobacteria Identification of Hoiamide A as an Inducer of Oxidative and Endoplasmic Reticulum Secretory Pathway Stress. Bonar, Sophia E Mattos, Daphne R Yu, Xinhui Neuhaus, George F Youssef, Diaa T A Shaala, Lamiaa A Gerwick, William H McPhail, Kerry L Ishmael, Jane E Humans Endoplasmic Reticulum Stress Oxidative Stress Endoplasmic Reticulum Depsipeptides Molecular Structure Secretory Pathway Superoxide Dismutase-1 Cell Line, Tumor Transcription Factor CHOP Cyanobacteria The endoplasmic reticulum (ER) to Golgi secretory compartment of eukaryotic cells is highly sensitive to changes in intracellular homeostasis. Using a primary screening assay that monitors the function of this pathway, we prioritized a cyanobacterial extract from the Red Sea that decreased secretion of a bioluminescent reporter, luciferase (GLuc), in living cells. A comparison of LCMS2 data against the GNPS database revealed a match for macrocyclic depsipeptide hoiamide A (). Biological testing confirmed the ability of to induce a mixed, non-lethal stress response in human U87-MG glioblastoma cells; analysis of stress markers by qRT-PCR revealed early upregulation of superoxide dismutase 1 (SOD1) and C/EBP-homologous protein (CHOP) relative to the control. Co-treatment of cells with (100 nM to 3 μM) and antioxidant -acetylcysteine afforded full protection from -induced decreases in GLuc secretion. We report that terminally differentiated human SH-SY5Y neuroblastoma cells, with a neuron-like phenotype, are highly sensitive to nanomolar concentrations of , whereas undifferentiated cells remained viable at 3 μM. These results expand the known biology of hoiamides and suggest that neurotoxic potential of is likely due to an inherent failure of neurons to adapt to the loss of redox homeostasis and sustained ER stress. |
| title | Identification of Hoiamide A as an Inducer of Oxidative and Endoplasmic Reticulum Secretory Pathway Stress. |
| topic | Humans Endoplasmic Reticulum Stress Oxidative Stress Endoplasmic Reticulum Depsipeptides Molecular Structure Secretory Pathway Superoxide Dismutase-1 Cell Line, Tumor Transcription Factor CHOP Cyanobacteria |
| url | https://pubmed.ncbi.nlm.nih.gov/42080225/ |