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

Abstract

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.

S-Allylmercapro-N-Acetylcysteine Attenuates the Oxidation-Induced Lens Opacification and Retinal Pigment Epithelial Cell Death In Vitro

“…This ASSNAC-induced Nrf2 activation increased the expression of phase II detoxifying enzymes, including the cystine transporter (xCT), which provides cells with free cysteine as a substrate for glutathione biosynthesis. Thus, ASSNAC dual anti-oxidant activity includes increased cellular availability of cysteine (via released NAC and up-regulated cysteine transporter activity) and up-regulated phase II-induced enzymes for glutathione biosynthesis, both leading to significant increase in glutathione cellular level, resulting in significant augmentation of cells [20] and of the entire organism [21] resistance to oxidative stress. Indeed, our further study demonstrated a protective role for ASSNAC against oxidative stress, as it attenuated the clinical symptoms in experimental autoimmune encephalomyelitis (EAE), which serves as a mouse model for multiple sclerosis [22].…”

Anti-Aging Effect of Hemerocallis citrina Baroni Polysaccharide-Rich Extract on Caenorhabditis elegans

“…Among these, gst-4 is related to glutathione metabolism, and gst-7 is related to innate immunity. They are all homologous to human hematopoietic prostaglandin D synthase gene [ 42 , 43 ]. gst-10 is orthologous to human glutathione S-transferase pi 1, which plays an important role in the regulation of life span and thermal acclimatization [ 44 ].…”

SUMO-mediated regulation of a H3K4me3 reader controls germline development inC. elegans

“…Lifespan assays were performed using regular NGM plates seeded with OP50 at 20°C, as previously described, but with some alterations [77]. Briefly, gravid adults were bleached three consecutive times prior to the assays.…”