Regional Distribution of Homocysteine in the Mammalian Brain

The regional distribution of L-homocysteine (Hcy) was determined in brains from mouse, rat, guinea pig, and rabbit, using a sensitive radioenzymatic assay. Large interspecies variations in the Hcy content in various parts of the brain were observed, but cerebellum contained the highest amount in all species investigated. In the rat the amount of Hcy in cerebellum (6.4 nmol/g) was about sixfold higher than in most other parts of the brain, whereas in the mouse and guinea pig the amount in cerebellum (about 1 nmol/g) was only twofold higher than in the other brain regions. There was a remarkably high level of Hcy in all regions of the rabbit brain (4-10 nmol/g); the highest concentration was found in the cerebellar white matter. In this species the amount of Hcy in all brain regions examined exceeded that in the liver.     

Hippocampal electrical activity and gamma-aminobutyrate metabolism in brain tissue following administration of homocysteine

Abstract: The concentration of γ-aminobutyrate (GABA) and the activity of glutamate decarboxylase and GABA-transaminase were measured in extracts of mouse brain before the onset and during the course of generalized seizures induced by systemic administration of homocysteine thiolactone. The results indicate that whole brain GABA metabolism is unaffected by subconvulsive and convulsive doses of homocysteine at all stages of the generalized seizure. Electroencephalographic monitoring of rat brain electrical activity via hippocampal electrode implantation allowed the course of homocysteine-induced seizures to be followed and afforded a means of quantifying such seizures.     

The effect of homocysteine thiolactone and its alpha methylated derivative on bone matrix in the mouse

Summary Homocysteine (HC) is a radiation protector but toxic to bone. Its derivative homocysteine thiolactone (HCTL) and the alpha-alkylated analogue (A-methyl-HCTL) was fed to mice for a period of six weeks in a daily dose of 50 mg/kg body weight. Parameters for bone matrix as collagen content, acid solubility of bone collagen, urinary bone collagen cross links (pyridinolines) and urinary acid glycosaminoglycans were determined. Urinary acid glycosaminoglycans were significantly reduced in the HCTL treated group but not in the alpha-methyl-homocysteine thiolactone (A-methyl-HCTL) group (controls: 45 ± 7 mg/mmol creatinine, homocysteine thiolactone 38 ± 5 mg/mmol creatinine, A-methyl HCTL 45 ± 6 mg/mmol creatinine).No differences were found for the parameters of bone collagen between the groups. The potent radiation protecting methylated derivative therefore did not change bone matrix and should be a candidate for further toxicological studies.     

Transsulphuration and methylation of homocysteine in control and mutant human fibroblasts

The ability of human skin-fibroblasts in monolayer culture to carry out transsulphuration and remethylation of homocysteine has been tested. The conversion of homocyst(e)ine to cyst(e)ine and methionine was studied in control and mutant cells by incubation for 16 h with l-[³⁵S]homocystine. Labelled cysteic acid and methionine sulphone were found in hydrolysates of oxidized cell proteins. The quantities found were dependent on the time of incubation and were used as a measure of cyst(e)ine and methionine formation, respectively. In control cells, labelled cyst(e)ine and labelled methionine were found. In cystathionine β-synthase-deficient cell lines, labelled cyst(e)ine formation was reduced, while labelled methionine formed was similar to that of controls, indicating the role of transsulphuration in the formation of cyst(e)ine observed in control cells. In a 5,10-methylenetetrahydrofolate reductase-deficient cell line, labelled methionine formation was reduced, indicating the role of N-5-methyltetrahydrofolate-requiring methylation of homocysteine in the formation of methionine observed in control cells.     

Homocysteine inhibits endothelial progenitor cells proliferation via DNMT1-mediated hypomethylation of Cyclin A

Endothelial progenitor cells (EPCs) contribute to neovasculogenesis and reendothelialization of damaged blood vessels to maintain the endothelium. Dysfunction of EPCs is implicated in the pathogenesis of vascular injury induced by homocysteine (Hcy). We aimed to investigate the role of Cyclin A in Hcy-induced EPCs dysfunction and explore its molecular mechanism. In this study, by treatment of EPCs with Hcy, we found that the expression of Cyclin A mRNA and protein were significantly downregulated in a dose-dependent manner. Knockdown of Cyclin A prominently reduced proliferation of EPCs, while over-expression of Cyclin A significantly promoted the cell proliferation, suggesting that Hcy inhibits EPCs proliferation through downregulation of Cyclin A expression. In addition, epigenetic study also demonstrated that Hcy induces DNA hypomethylation of the Cyclin A promoter in EPCs through downregulated expression of DNMT1. Moreover, we found that Hcy treatment of EPCs leads to increased SAM, SAH and MeCP2, while the ratio of SAM/SAH and MBD expression decrease. In summary, our results indicate that Hcy inhibits Cyclin A expression through hypomethylation of Cyclin A and thereby suppress EPCs proliferation. These findings demonstrate a novel mechanism of DNA methylation mediated by DNMT1 in prevention of Hcy associated cardiovascular disease.     

同型半胱氨酸与冠心病

随着社会的进步以及人类生活水平的提高,冠心痛的发病率也逐年提高,目前已经成为全球死亡率最高的疾病之一,同时医学水平的不断发展也使得人们对冠心病有了更进一步的研究.近年来同型半胱氨酸越来越受到人们的关注,众多研究表明,高同型半胱氨酸血症是冠心痛的独立危险因子,可以影响冠心病的严重程度及预后.但是迄今为止,同型半胱氨酸在冠心病发病中的确切机制尚不完全明确,认为主要与血管内皮损伤、血管平滑肌细胞增殖凋亡、破坏凝血纤溶系统、影响糖、蛋白质、脂质代谢等方面有关.针对高同型半胱氨酸血症的治疗,对于改善冠心病患者的预后有一定疗效.因此,本文就同型半胱氨酸冠心痛的关系作一综述,从而为临床更好的防治冠心痛提供相关的资料.     

血清同型半胱氨酸、叶酸、维生素B12水平与冠状动脉病变严重程度的相关性分析

摘要 目的：探讨血清同型半胱氨酸(homocysteine, Hcy)、叶酸、维生素B12水平与冠状动脉病变严重程度的相关性。方法：选取经冠脉造影检查确诊的稳定期冠心病患者220例为研究组,并以同期健康查体志愿者100例为对照组。检测和比较两组血清Hcy、叶酸、维生素B12和N -末端脑钠肽前体(N-terminal brain natriuretic peptide precursor,NT-proBNP)水平。研究组根据冠脉造影情况进行SYNTAX评分评价,通过心脏超声检查检测左室射血分数(left ventricular ejection fraction,LVEF),确定冠脉病变严重程度。比较研究组SYNTAX低分组(1～22分)、中分组(23～32分)和高分组(≥33分)患者上述各指标水平,并分析研究组血清Hcy、叶酸、维生素B12水平与其血清NT-proBNP 水平、SYNTAX评分和LVEF的关系。结果：与对照组比较,研究组血清Hcy和NT-proBNP水平升高而血清叶酸、维生素B12水平降低(P＜0.05)。研究组SYNTAX评分和LVEF分别为(28.76±6.58)分和(47.33±8.66)%,SYNTAX中分和高分患者血清Hcy和NT-proBNP水平高于SYNTAX低分患者而血清叶酸、维生素B12水平和LVEF则低于SYNTAX低分患者,SYNTAX高分患者血清Hcy和NT-proBNP水平高于SYNTAX中分患者而血清叶酸、维生素B12水平和LVEF则低于SYNTAX中分患者(P＜0.05)。Pearson线性相关分析结果显示研究组血清Hcy水平与其血清NT-proBNP 水平、SYNTAX评分均呈正相关(r=0.881,0.793,P＜0.05),与其LVEF则呈负相关(r=-0.876,P＜0.05);而其血清叶酸、维生素B12水平与其血清NT-proBNP 水平、SYNTAX评分均呈负相关(叶酸：r=-0.786,-0.825;维生素B12：r=-0.884,-0.818,P＜0.05),与其LVEF则呈正相关(r=0.893,0.859,P＜0.05)。结论：血清Hcy是冠心病的重要危险因素,其水平随着冠状动脉病变程度加重而升高;血清叶酸、维生素B12是冠心病的保护因素,其水平随着冠状动脉病变程度加重而降低。     

免疫球蛋白联合B族维生素对癫痫症状及生活质量的影响

目的:探讨免疫球蛋白联合B族维生素对癫痫症状及生活质量的影响.方法:2017年2月至2020年1月选择在本院诊治的癫痫患者78例,根据随机数字表法把患者分为观察组与对照组各39例.两组都给予常规治疗,对照组给予维生素B12治疗,观察组给予免疫球蛋白联合维生素B12治疗,记录两组治疗后症状与生活质量情况.结果:治疗后观察...     

急性脑梗死患者血浆同型半胱氨酸水平及其相关因素分析*

目的:探讨急性脑梗死患者血浆同型半胱氨酸水平及相关因素。方法:采用高效液相色谱法检测232例急性脑梗死患者血浆Hcy水平,并对其相关因素进行统计学分析。结果:急性脑梗死组患者血浆Hcy水平明显升高(P<0.05);并与叶酸及维生素B12水平显著相关。不同年龄段急性脑梗死患者血浆Hcy水平具有差异。并与颈动脉粥样硬化斑块相关联。结论:血浆Hcy水平增高是脑梗死的危险因素之一,并与患者年龄、血液中叶酸、维生素B12水平及脑梗死性质相关联。     

Structure and function of S-adenosylhomocysteine hydrolase

In mammals, S-adenosylhomocysteine hydrolase (AdoHcyase) is the only known enzyme to catalyze the breakdown of S-adenosylhomocysteine (AdoHcy) to homocysteine and adenosine. AdoHcy is the product of all adenosylmethionine (AdoMet)-dependent biological transmethylations. These reactions have a wide range of products, and are common in all facets of biometabolism. As a product inhibitor, elevated levels of AdoHcy suppress AdoMet-dependent transmethylations. Thus, AdoHcyase is a regulator of biological transmethylation in general. The three-dimensional structure of AdoHcyase complexed with reduced nicotinamide adenine dinucleotide phosphate (NADH) and the inhibitor (1′R, 2′S, 3′R)-9-(2′,3′-dihyroxycyclopenten-1-yl)adenine (DHCeA) was solved by a combination of the crystallographic direct methods program, SnB, to determine the selenium atom substructure and by treating the multiwavelength anomalous diffraction data as a special case of multiple isomorphous replacement. The enzyme architecture resembles that observed for NAD-dependent dehydrogenases, with the catalytic domain and the cofactor binding domain each containing a modified Rossmann fold. The two domains form a deep active site cleft containing the cofactor and bound inhibitor molecule. A comparison of the inhibitor complex of the human enzyme and the structure of the rat enzyme, solved without inhibitor, suggests that a 17° rigid body movement of the catalytic domain occurs upon inhibitor/substrate binding.