Twelve-week-old male CBS<sup>+/-</sup> (a model of HHcy) and sibling CBS<sup>+/+</sup> (WT) mice were treated with SG1002 (a slow release H<sub>2</sub>S donor) diet for 4 months.
Cystathionine-beta-synthase (CBS) is an enzyme that catalyzes the first step of the transsulfuration pathway, from homocysteine to cystathionine, and in which variations are associated with human hyperhomocysteinemia and homocystinuria.
Stratified analysis by sex found that lower CBS methylation levels were associated with a 2.128-fold increased risk for treatment failure in males with HHcy.
In vitro study also shows that HMD induced hyperhomocysteinemia (HHcy) impaired both adhesion and angiogenesis properties of BM-EPCs, accompanied by higher methylation level of CBS promoter that compared to control.
NaHS adminstration restored the decreased levels of H<sub>2</sub>S and polysulfides with a concomitant increase in the activity of cystathionase (CSE) and cystathionine β-synthase (CBS) in the brain regions of HHcy animals.
The aim of this study was to determine the effect of whole eggs and egg components (i.e., egg protein and choline) with respect to 1) homocysteine balance and 2) the hepatic expression and activity of betaine-homocysteine S-methyltransferase (BHMT) and cystathionine β-synthase (CBS) in a folate-restricted (FR) rat model of hyperhomocysteinemia.
Redox homeostasis, free-radical detoxification and one-carbon metabolism (Methionine-Hcy-Folate cycle) require CBS and its deficiency leads to hyperhomocysteinemia (HHcy) causing retinovascular thromboembolism and eye-lens dislocation along with vascular cognitive impairment and dementia.
To study Hyperhomocysteinemia (HHcy)-induced epigenetic modifications as potential mechanisms of blood retinal barrier (BRB) dysfunction, retinas isolated from three- week-old mice with elevated level of Homocysteine (Hcy) due to lack of the enzyme cystathionine β-synthase (<i>cbs<sup>-/-</sup></i> , <i>cbs<sup>+/-</sup></i> and <i>cbs<sup>+/+</sup></i> ), human retinal endothelial cells (HRECs), and human retinal pigmented epithelial cells (ARPE-19) treated with or without Hcy were evaluated for (1) histone deacetylases (HDAC), (2) DNA methylation (DNMT), and (3) miRNA analysis.
This is the first report from Pakistan where novel as well as recurrent CBS mutations causing hyperhomocysteinemia and lens dislocation in three patients from different families are being reported with the predicted effect of the risk allele of the MTHFR SNP in causing hyperhomocysteinemia.
These results highlighted that deficiency of CBS activity was correlated with the nitration of CBS at Tyr<sup>163</sup>, Tyr<sup>223</sup>, Tyr<sup>381</sup> and Tyr<sup>518</sup>, which may play a mutual role in the progression of HHcy.
Mild (22 µmol/L) and moderate (88 µmol/L) HHcy were induced in cystathionine β-synthase wild-type (Cbs(+/+)) and heterozygous-deficient (Cbs(-/+)) mice by a high-methionine (HM) diet.
We studied the effect of HHcy on PCs and its role in vascular repair in severe HHcy (∼150 μM), which was induced in cystathionine-β synthase heterozygous mice fed a high-methionine diet for 8 weeks.
In patients with CVT, plasma total homocysteine measurement as part of the etiologic work up may reveal severe hyperhomocysteinemia due to CBS or remethylation defects that require specific treatment and management including perhaps protein-restricted diet and/or vitamin therapy for life.
Protective effect towards hyperhomocysteinemia was observed with heterozygous (ancestral/insertion) genotype of CBS844ins68 compared to homozygous ancestral type [OR (95% CI); 0.58 (0.34-0.99)].
Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) and cystathionine β-synthase (CBS) genes, involved in the intracellular metabolism of homcysteine, can result in hyperhomocysteinemia.
Deficiency in cystathionine beta synthase (CBS) enzyme sometimes leads to hyperhomocysteinemia/homocystinuria, conditions often associated with mental retardation (MR).
In humans, severe hyperhomocysteinemia due to genetic alterations in cystathionine beta-synthase (Cbs) or methylenetetrahydrofolate reductase (Mthfr) results in neurological abnormalities and premature death from vascular complications.
Furthermore, we characterized monocyte heterogeneity in Tg-hCBS apoE(-/-) Cbs(-/-) mice and another severe HHcy mouse model (Tg-S466L Cbs(-/-)) with a disease-relevant mutation (Tg-S466L) that lacks hyperlipidemia.