Protective Effects of Ursolic Acid Against Cytotoxicity Induced by Corticosterone: Role of Protein Kinases
| Autor: | Isabella A. Heinrich, Manuella P. Kaster, Andiara E. Freitas, Rodrigo B. Leal, Nicolle Platt, Ana Lúcia S. Rodrigues, Manuela G. López, Ana B. Ramos-Hryb |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Kinase General Medicine Pharmacology Biochemistry 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Chelerythrine chemistry Ca2+/calmodulin-dependent protein kinase LY294002 Viability assay Protein kinase A Cytotoxicity 030217 neurology & neurosurgery Protein kinase C |
| Zdroj: | Neurochemical research. |
| ISSN: | 1573-6903 |
| Popis: | Neuronal hippocampal death can be induced by exacerbated levels of cortisol, a condition usually observed in patients with Major depressive disorder (MDD). Previous in vitro and in vivo studies showed that ursolic acid (UA) elicits antidepressant and neuroprotective properties. However, the protective effects of UA against glucocorticoid-induced cytotoxicity have never been addressed. Using an in vitro model of hippocampal cellular death induced by elevated levels of corticosterone, we investigated if UA prevents corticosterone-induced cytotoxicity in HT22 mouse hippocampal derived cells. Concentrations lower than 25 µM UA did not alter cell viability. Co-incubation with UA for 48 h was able to protect HT22 cells from the reduction on cell viability and from the increase in apoptotic cells induced by corticosterone. Inhibition of protein kinase A (PKA), protein kinase C (PKC) and, Ca2+/calmodulin-dependent protein kinase II (CaMKII), but not phosphoinositide 3-kinase(PI3K), by using the pharmacological the inhibitors: H-89, chelerythrine, KN-62, and LY294002, respectively totally abolished the cytoprotective effects of UA. Finally, UA abrogated the reduction in phospho-extracellular signal–regulated kinases 1 and 2 (ERK1/2) but not in phospho-c-Jun kinases induced by corticosterone. These results indicate that the protective effect of UA against the cytotoxicity induced by corticosterone in HT22 cells may involve PKA, PKC, CaMKII, and ERK1/2 activation. The cytoprotective potential of UA against corticosterone-induced cytotoxicity and its ability to modulate intracellular signaling pathways involved in cell proliferation and survival suggest that UA may be a relevant strategy to manage stress-related disorders such as MDD. |
| Databáze: | OpenAIRE |
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