Cystathionine β-synthase-derived hydrogen sulfide regulates lipopolysaccharide-induced apoptosis of the BRL rat hepatic cell line in vitro

Abstract

Hydrogen sulfide (H2S), is a member of the novel family of endogenous gaseous transmitters, termed “gasotransmitters exhibiting diverse physiological activities, and is generated in mammalian tissues mainly by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3MST) in conjunction with cysteine (aspartate) aminotranferase (CAT). The distributions of these enzymes are species- and tissue-specific. The liver, as the main organ that generates H2S in vivo, functions in biotransformation and metabolism. However, the liver is vulnerable to damage from internal and external factors, including inflammatory mediators, drugs and poisons. The present study evaluated the endogenous CBS-H2S synthesis regulating lipopolysaccharide (LPS)-induced apoptosis of hepatic cells. The rat hepatic cell line, BRL, was incubated with LPS for various time periods to establish a cell-damage model. Incubation with LPS resulted in a significant increase in CBS expression and H2S production. It also stimulated apoptosis and decreased the mitochondrial membrane potential. Pretreatment with the CBS inhibitor aminooxyacetic acid (AOAA) or CBS small interfering RNA (siRNA) decreased LPS-enhanced H2S production. Notably, apoptosis increased for a short period and then decreased gradually, while the mitochondrial membrane potential demonstrated the opposite trend. These results showed that endogenous CBS-H2S synthesis demonstrated early anti-apoptotic activity and subsequent pro-apoptotic activity in LPS-induced apoptosis. These results suggest a new approach for developing novel drugs for this condition.

Switching the intracellular pathway and enhancing the therapeutic efficacy of small interfering RNA by auroliposome

“…2E). These results are consistent with the previously published data showing silencing of target genes (e.g., MICU1 and CBS) within the dose range 50 to 200 nM depending on the cell type, type of siRNAs, and target genes and transfection reagents used (12,21,(31)(32)(33). Hybrid nanomaterials can yield not only the beneficial features of the individual components but also unique benefits arising from the combination (14,30).…”

Transcriptome dynamics in the asexual cycle of the chordate Botryllus schlosseri

“…In mammals, cullin-1 is involved in the regulation of neuronal apoptosis [ 69 ] whereas cystationine ß-synthase regulates LPS-induced apoptosis in hepatic cells [ 70 ]. Homologous genes for cullin-1 and cystationine ß-synthase are present in our transcriptomes and the variation of their transcription supports the hypothesis of their involvement in apoptosis regulation during the B. schlosseri blastogenetic cycle.…”

Identification of Cystathionine β‐Synthase Inhibitors Using a Hydrogen Sulfide Selective Probe

“…Despite the poor potency and selectivity of these compounds, aminooxyacetate and hydroxylamine are routinely employed as CBS inhibitors in biological studies 9. 10 It is clear that the availability of probes with improved potency and selectivity would be of great value in understanding the biological roles of this important enzyme.…”