ArticleJournal of lipid research2014
Effect of procysteine on aging-associated changes in hepatic GSH and SMase: evidence for transcriptional regulation of smpd3.
Article in Journal of lipid research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Effect of the cysteine prodrug L-2-oxothiazolidine-4-carboxylic acid onFrontiers in toxicology · 2026Article
- Hepatic sphingomyelin phosphodiesterase 3 promotes steatohepatitis by disrupting membrane sphingolipid metabolism.Cell metabolism · 2025Article
- Impact of HepG2 Cells Glutathione Depletion on Neutral Sphingomyelinases mRNA Levels and Activity.Current issues in molecular biology · 2023Article
- Protective effects and mechanisms of Lizhong decoction against non-alcoholic fatty liver disease in a rat model.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2022Article
- Cysteine Donor-Based Brain-Targeting Prodrug: Opportunities and Challenges.Oxidative medicine and cellular longevity · 2022Review
- Neutral sphingomyelinase-2 and cardiometabolic diseases.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2021Review
- A Novel Combination of Fruits and Vegetables Prevents Diet-Induced Hepatic Steatosis and Metabolic Dysfunction in Mice.The Journal of nutrition · 2020Article
- Future treatments for hyperoxaluria.Current opinion in urology · 2020Review
- Associations of severity of fatty liver with oxidative stress, SAA, CRP and degree of cerebral arteriosclerosis in cerebral arteriosclerosis patients who have fatty liver.International journal of clinical and experimental pathology · 2019Article
- Article
- AMPK activation by liquiritigenin inhibited oxidative hepatic injury and mitochondrial dysfunction induced by nutrition deprivation as mediated with induction of farnesoid X receptor.European journal of nutrition · 2017Article
- Increasing adipocyte lipoprotein lipase improves glucose metabolism in high fat diet-induced obesity.The Journal of biological chemistry · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
In hepatocytes, aging-associated decline in GSH has been linked to activation of neutral SMase (nSMase), accumulation of bioactive ceramide, and inflammation. In this study, we seek to test whether dietary supplementation with the cysteine precursor, L-2-oxothiazolidine-4-carboxylic acid (OTC), would correct the aging-associated differences in hepatic GSH, nSMase, and ceramide. Young and aged mice were placed on a diet that either lacked sulfur-containing amino acids (SAAs) or had 0.5% OTC for 4 weeks. Mice fed standard chow were used as an additional control. SAA-deficient mice exhibited significant aging-associated differences in hepatic GSH, GSH/GSSG, ceramide, and nSMase. C24:1 ceramide, the major ceramide species in liver, was affected the most by aging, followed by the less abundant C16:0 ceramide. OTC supplementation eliminated the aging-associated differences in hepatic GSH and GSH/GSSG ratio. Surprisingly, however, instead of decreasing, the nSMase activity and ceramide increased in the OTC-fed mice irrespective of their age. These effects were due to elevated nSMase-2 mRNA and protein and appeared to be direct. Similar increases were seen in HepG2 cells following treatment with OTC. The OTC-fed aged mice also exhibited hepatic steatosis and triacylglyceride accumulation. These results suggest that OTC is a potent stimulant of nSMase-2 expression and that there may be unanticipated complications of OTC supplementation.
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