Potential neuroprotective and anti-apoptotic properties of a long-lasting stable analog of ghrelin: an in vitro study using SH-SY5Y cells
Language English Country Czech Republic Media print-electronic
Document type Journal Article
PubMed
29303606
DOI
10.33549/physiolres.933761
PII: 933761
Knihovny.cz E-resources
- MeSH
- Apoptosis drug effects MeSH
- Ghrelin analogs & derivatives pharmacology MeSH
- Glycolysis drug effects MeSH
- L-Lactate Dehydrogenase metabolism MeSH
- Humans MeSH
- MAP Kinase Signaling System drug effects MeSH
- Membrane Potential, Mitochondrial drug effects MeSH
- Cell Line, Tumor MeSH
- Neuroprotective Agents pharmacology MeSH
- Neurotoxicity Syndromes prevention & control MeSH
- Apoptosis Regulatory Proteins biosynthesis genetics MeSH
- Pyruvaldehyde toxicity MeSH
- Receptors, Ghrelin biosynthesis MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Ghrelin MeSH
- Ghsr1a protein, human MeSH Browser
- L-Lactate Dehydrogenase MeSH
- Neuroprotective Agents MeSH
- Apoptosis Regulatory Proteins MeSH
- Pyruvaldehyde MeSH
- Receptors, Ghrelin MeSH
Neurodegenerative disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD), are increasing in prevalence. Currently, there are no effective and specific treatments for these disorders. Recently, positive effects of the orexigenic hormone ghrelin on memory and learning were demonstrated in mouse models of AD and PD. In this study, we tested the potential neuroprotective properties of a stable and long-lasting ghrelin analog, Dpr(3)ghrelin (Dpr(3)ghr), in SH-SY5Y neuroblastoma cells stressed with 1.2 mM methylglyoxal (MG), a toxic endogenous by-product of glycolysis, and we examined the impact of Dpr(3)ghr on apoptosis. Pre-treatment with both 10(-5) and 10(-7) M Dpr(3)ghr resulted in increased viability in SH-SY5Y cells (determined by MTT staining), as well as reduced cytotoxicity of MG in these cells (determined by LDH assay). Dpr(3)ghr increased viability by altering pro-apoptotic and viability markers: Bax was decreased, Bcl-2 was increased, and the Bax/Bcl-2 ratio was attenuated. The ghrelin receptor GHS-R1 and Dpr(3)ghr-induced activation of PBK/Akt were immuno-detected in SH-SY5Y cells to demonstrate the presence of GHS-R1 and GHS-R1 activation, respectively. We demonstrated that Dpr(3)ghr protected SH-SY5Y cells against MG-induced neurotoxicity and apoptosis. Our data suggest that stable ghrelin analogs may be candidates for the effective treatment of neurodegenerative disorders.
References provided by Crossref.org
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