S-allylmercapto-N-acetylcysteine protects against oxidative stress and extends lifespan in Caenorhabditis elegans

Autor: Limor Broday, Amir Levine, Naphtali Savion, Ulrike Bening Abu-Shach, Shlomo Kotev-Emeth
Rok vydání: 2018
Předmět:
0301 basic medicine
Antioxidant
Nematoda
medicine.medical_treatment
Gene Expression
lcsh:Medicine
Drug research and development
medicine.disease_cause
Biochemistry
Antioxidants
chemistry.chemical_compound
Clinical trials
0302 clinical medicine
Gene expression
lcsh:Science
Caenorhabditis elegans
Glutathione Transferase
Multidisciplinary
Strain (chemistry)
biology
Chromatographic Techniques
Temperature
Eukaryota
Animal Models
Glutathione
6. Clean water
Up-Regulation
Allyl Compounds
Experimental Organism Systems
Amino Acid Specific Chromatography
Phase II clinical investigation
Research Article
Imaging Techniques
Longevity
Research and Analysis Methods
Protective Agents
Agar plate
03 medical and health sciences
Model Organisms
Fluorescence Imaging
Glutathione Chromatography
Genetics
medicine
Animals
Caenorhabditis elegans Proteins
Medicine and health sciences
Pharmacology
Affinity Chromatography
lcsh:R
Organisms
Biology and Life Sciences
Cell Biology
Hydrogen Peroxide
biology.organism_classification
Invertebrates
Molecular biology
Enzyme assay
Acetylcysteine
Oxidative Stress
030104 developmental biology
chemistry
Clinical medicine
Caenorhabditis
biology.protein
lcsh:Q
Peptides
030217 neurology & neurosurgery
Oxidative stress
Zdroj: PLoS ONE, Vol 13, Iss 3, p e0194780 (2018)
PLoS ONE
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0194780
Popis: S-allylmercapto-N-acetylcysteine (ASSNAC) was shown in our previous study to activate Nrf2-mediated processes and increase glutathione level and resistance to oxidative stress in cultured endothelial cells. In this study, we explored the antioxidant protective effect of ASSNAC in Caenorhabditis elegans (C. elegans). Treatment of gst-4 reporter strain (CL2166) with increasing concentrations of ASSNAC (0.2 to 20 mM) for 24 hours and with ASSNAC (10 mM) for various time periods demonstrated a significant concentration- and time-dependent increase in Glutathione S-transferase (GST) gene expression (up to 60-fold at 20 mM after 24 hours). In addition, ASSNAC (2 mM; 24 hours) treatment of C. elegans strains N2 (wild type strain), gst-4 reporter (CL2166) and temperature sensitive sterile strain (CF512) significantly increased GST enzyme activity by 1.9-, 1.5- and 1.8-fold, respectively. ASSNAC (2.0 mM; 24 hours) increased the reduced glutathione content in N2 and CF512 strains by 5.9- and 4.9-fold, respectively. Exposure of C. elegans (N2 strain) to a lethal concentration of H2O2 (3.5 mM; 120 min) resulted in death of 88% of the nematodes while pretreatment with ASSNAC (24 hours) reduced nematodes death in a concentration-dependent manner down to 8% at 2.0 mM. C. elegans nematodes (strain CF512) cultured on agar plates containing ASSNAC (0.5 to 5.0 mM) demonstrated a significant increase in lifespan compared to control (mean lifespan 26.45 ± 0.64 versus 22.90 ± 0.59 days; log-rank p ≤ 0.001 at 2.0 mM) with a maximal lifespan of 40 versus 36 days. In conclusion, ASSNAC up-regulates the GST gene expression and enzyme activity as well as the glutathione content in C. elegans nematodes and thereby increases their resistance to oxidative stress and extends their lifespan.
Databáze: OpenAIRE
Externí odkaz: