Propargylglycine inhibits hypotaurine/taurine synthesis and elevates cystathionine and homocysteine concentrations in primary mouse hepatocytes.
Propargylglycine inhibits hypotaurine/taurine synthesis and elevates cystathionine and homocysteine concentrations in primary mouse hepatocytes.
复制标题
presparlglycine抑制下龙/牛磺酸的合成，并升高原发性小鼠肝细胞中的胱淀粉和同型半胱氨酸的浓度。
DOI：
10.1007/s00726-015-1948-7
复制
发表时间：
2015-06
期刊：
影响因子：
3.5
通讯作者：
Roman, Heather B.
中科院分区：
文献类型：
--
作者：
Jurkowska, Halina;Stipanuk, Martha H.;Hirschberger, Lawrence L.;Roman, Heather B.
我们的研究表明，从半胱氨酸双加氧酶敲除小鼠（Cdo1−/−）分离的肝细胞比Cdo1 +/+肝细胞具有更低水平的次牛磺酸和牛磺酸。有趣的是，次牛磺酸在培养的野生型肝细胞中积累。与未处理的肝细胞相比，dl-丙基甘氨酸（PPG，半胱硫氨酸γ-裂解酶和H2S生成抑制剂）显著降低了野生型肝细胞中的牛磺酸和次牛磺酸水平。添加2 mM PPG导致细胞内牛磺酸水平下降：从对照组的10.25±5.00下降到2.53±0.68 nmol/mg蛋白（培养24 h），从17.06±9.40下降到2.43±0.26 nmol/mg蛋白（对照与PPG； 48 h）。PPG的加入也降低了细胞内低氨基磺酸水平：从7.46±3.55降至0.31±0.12 nmol/mg蛋白质（对照组与PPG相比，24小时），从4.54±3.20降至0.42±0.11 nmol/mg蛋白质（对照组与PPG相比，48小时）。在培养基中观察到PPG对次牛磺酸和牛磺酸水平的类似影响。PPG阻断了野生型肝细胞中次牛磺酸/牛磺酸的合成，表明PPG对半胱氨酸磺酸脱羧酶（吡哆醛5′-磷酸依赖酶）和半胱硫氨酸γ-裂解酶有较强的抑制作用。在PPG存在的情况下，野生型和Cdo1−/−细胞内和培养基中胱硫氨酸水平均升高。同型半胱氨酸或蛋氨酸的加入导致细胞内同型半胱氨酸浓度升高，而同型半胱氨酸是胱氨酸β-合成酶（CBS）的共底物。PPG似乎通过提高肝细胞的同型半胱氨酸水平来增加cbs介导的脱硫作用。PPG或基因型对细胞内或培养基谷胱甘肽水平没有总体影响。
Our investigation showed that hepatocytes isolated from cysteine dioxygenase knockout mice (Cdo1−/−) had lower levels of hypotaurine and taurine than Cdo1 +/+ hepatocytes. Interestingly, hypotaurine accumulates in cultured wild-type hepatocytes. dl-propargylglycine (PPG, inhibitor of cystathionine γ-lyase and H2S production) dramatically decreased both taurine and hypotaurine levels in wild-type hepatocytes compared to untreated cells. Addition of 2 mM PPG resulted in the decrease of the intracellular taurine levels: from 10.25 ± 5.00 observed in control, to 2.53 ± 0.68 nmol/mg protein (24 h of culture) and from 17.06 ± 9.40 to 2.43 ± 0.26 nmol/mg protein (control vs. PPG; 48 h). Addition of PPG reduced also intracellular hypotaurine levels: from 7.46 ± 3.55 to 0.31 ± 0.12 nmol/mg protein (control vs. PPG; 24 h) and from 4.54 ± 3.20 to 0.42 ± 0.11 nmol/mg protein (control vs. PPG; 48 h). The similar effects of PPG on hypotaurine and taurine levels were observed in culture medium. PPG blocked hypotaurine/taurine synthesis in wild-type hepatocytes, suggesting that it strongly inhibits cysteinesulfinate decarboxylase (pyridoxal 5′-phosphate-dependent enzyme) as well as cystathionine γ-lyase. In the presence of PPG, intracellular and medium cystathionine levels for both wild-type and Cdo1 −/− cells were increased. Addition of homocysteine or methionine resulted in higher intracellular concentrations of homocysteine, which is a cosubstrate for cystathionine β-synthase (CBS). It seems that PPG increases CBS-mediated desulfhydration by enhancing homocysteine levels in hepatocytes. There were no overall effects of PPG or genotype on intracellular or medium glutathione levels.
登录
查看更多内容
影响因子：
6.1
作者：
Deminice, Rafael;Rosa, Flavia Troncon;Jordao, Alceu Afonso
通讯作者：
Jordao, Alceu Afonso
DOI：
10.1016/0006-291x(75)90527-6
发表时间：
1975-01-01
影响因子：
3.1
作者：
FINKELSTEIN, JD;KYLE, WE;MARTIN, JJ
通讯作者：
MARTIN, JJ
影响因子：
6.6
作者：
Roman, Heather B.;Hirschberger, Lawrence L.;Stipanuk, Martha H.
通讯作者：
Stipanuk, Martha H.
影响因子：
4.8
作者：
Singh, Sangita;Padovani, Dominique;Banerjee, Ruma
通讯作者：
Banerjee, Ruma
DOI：
10.1016/s0378-4347(00)84599-5
发表时间：
1985-01-01
期刊：
JOURNAL OF CHROMATOGRAPHY
影响因子：
--
作者：
HIRSCHBERGER, LL;DELAROSA, J;STIPANUK, MH
通讯作者：
STIPANUK, MH