Sphingosine kinase 1-associated autophagy differs between neurons and astrocytes
| Autor: | Vivekananda Shetty, Chinnaswamy Jagannath, Chandrashekar R. Ambati, Jose F. Moruno-Manchon, Nagireddy Putluri, Louise D. McCullough, Andrey S. Tsvetkov, Ndidi Ese Uzor |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Cell type Huntingtin Immunology Cell Neuroprotection Article 03 medical and health sciences Cellular and Molecular Neuroscience Downregulation and upregulation medicine Autophagy Animals lcsh:QH573-671 Neurons biology Chemistry lcsh:Cytology 1. No poverty Neurotoxicity Cell Biology medicine.disease Cell biology Rats Phosphotransferases (Alcohol Group Acceptor) 030104 developmental biology medicine.anatomical_structure Sphingosine kinase 1 nervous system Organ Specificity Astrocytes biology.protein |
| Zdroj: | Cell Death & Disease Cell Death and Disease, Vol 9, Iss 5, Pp 1-13 (2018) |
| ISSN: | 2041-4889 |
| Popis: | Autophagy is a degradative pathway for removing aggregated proteins, damaged organelles, and parasites. Evidence indicates that autophagic pathways differ between cell types. In neurons, autophagy plays a homeostatic role, compared to a survival mechanism employed by starving non-neuronal cells. We investigated if sphingosine kinase 1 (SK1)-associated autophagy differs between two symbiotic brain cell types—neurons and astrocytes. SK1 synthesizes sphingosine-1-phosphate, which regulates autophagy in non-neuronal cells and in neurons. We found that benzoxazine autophagy inducers upregulate SK1 and neuroprotective autophagy in neurons, but not in astrocytes. Starvation enhances SK1-associated autophagy in astrocytes, but not in neurons. In astrocytes, SK1 is cytoprotective and promotes the degradation of an autophagy substrate, mutant huntingtin, the protein that causes Huntington’s disease. Overexpressed SK1 is unexpectedly toxic to neurons, and its toxicity localizes to the neuronal soma, demonstrating an intricate relationship between the localization of SK1’s activity and neurotoxicity. Our results underscore the importance of cell type-specific autophagic differences in any efforts to target autophagy therapeutically. |
| Databáze: | OpenAIRE |
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