Cadmium exposure alters metabolomics of sulfur-containing amino acids in rat testes
Cadmium exposure alters metabolomics of sulfur-containing amino acids in rat testes
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DOI：
10.1089/ars.2005.7.781
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发表时间：
2005-05-01
影响因子：
6.6
通讯作者：
Suematsu, M
中科院分区：
文献类型：
--
作者：
Sugiura, Y;Kashiba, M;Suematsu, M
本研究的目的是检查分布的胱硫醚β-合酶（CBS）和胱硫醚γ-裂解酶（CSE），硫化氢（H2S）生成酶，和代谢组学改变含硫氨基酸暴露于应激大鼠睾丸。免疫组化显示这两种酶的不同分布：CBS主要发生在Leydig细胞，也可检测到支持细胞和生殖细胞，而CSE是明显的支持细胞和未成熟的生殖细胞，涉及精原细胞。睾丸中CSE和CBS的含量并未因给予氯化镉（一种导致细胞凋亡的抗精子应激源）而改变。代谢组学分析辅助液相色谱质谱仪显示显着改变含硫氨基酸代谢：甲硫氨酸和半胱氨酸的量显着升高，同时降低S-腺苷高半胱氨酸和S-腺苷甲硫氨酸之间的比例，这表明扩大的再甲基化循环和加速甲基捐赠。尽管半胱氨酸显著增加，但H，S的量不变，导致镉处理的大鼠中H2S/半胱氨酸比率显著下降。在这种情况下，氧化型谷胱甘肽（GSSG）显着减少，而还原型谷胱甘肽（GSH）得到很好的保持，GSH/GSSG的比例因此升高。这些结果共同表明，镉诱导含硫氨基酸的代谢组学重塑，即使当CBS或CSE的蛋白质表达不明显。虽然这种重塑事件的详细机制仍然未知，但我们的研究表明，代谢组学分析是一种强有力的工具，可以确定调节整个代谢系统的关键酶促反应。
This study aimed to examine distribution of cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE), the hydrogen sulfide (H2S)-generating enzymes, and metabolomic alterations in sulfur-containing amino acids in rat testes exposed to stressors. Immunohistochemistry revealed distinct distribution of the two enzymes: CBS occurred mainly in Leydig cells and was also detectable in Sertoli cells and germ cells, whereas CSE was evident in Sertoli cells and immature germ cells involving spermatogonia. The amounts of CSE and CBS in testes did not alter in response to administration of cadmium chloride, an antispermatogenic stressor leading to apoptosis. Metabolome analyses assisted by liquid chromatography equipped with mass spectrometry revealed marked alterations in sulfur-containing amino acid metabolism: amounts of methionine and cysteine were significantly elevated concurrently with a decrease in the ratio between S-adenosylhomocysteine and S-adenosylmethionine, suggesting expansion of the remethylation cycle and acceleration of methyl donation. Despite a marked increase in cysteine, amounts of H,S were unchanged, leading to a remarkable decline of the H2S/cysteine ratio in the cadmium-treated rats. Under such circumstances, oxidized glutathione (GSSG) was significantly reduced, whereas reduced glutathione (GSH) was well maintained, and the GSH/GSSG ratio was consequently elevated. These results collectively showed that cadmium induces metabolomic remodeling of sulfur-containing amino acids even when the protein expression of CBS or CSE is not evident. Although detailed mechanisms for such a remodeling event remain unknown, our study suggests that metabolomic analyses serve as a powerful tool to pinpoint a critical enzymatic reaction that regulates metabolic systems as a whole.