| Cadmium exposure alters metabolomics of sulfur-containing amino acids in rat testes. | |
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MedLine Citation:
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PMID: 15890025 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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This study aimed to examine distribution of cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE), the hydrogen sulfide (H(2)S)-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 Sadenosylmethionine, suggesting expansion of the remethylation cycle and acceleration of methyl donation. Despite a marked increase in cysteine, amounts of H(2)S were unchanged, leading to a remarkable decline of the H(2)S/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. |
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Authors:
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Yasoo Sugiura; Misato Kashiba; Kayo Maruyama; Koichi Hoshikawa; Ryoko Sasaki; Kazuyoshi Saito; Hideo Kimura; Nobuhito Goda; Makoto Suematsu |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Antioxidants & redox signaling Volume: 7 ISSN: 1523-0864 ISO Abbreviation: Antioxid. Redox Signal. Publication Date: 2005 May-Jun |
Date Detail:
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Created Date: 2005-05-13 Completed Date: 2005-09-27 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 100888899 Medline TA: Antioxid Redox Signal Country: United States |
Other Details:
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Languages: eng Pagination: 781-7 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Integrative Medical Biology, School of Medicine, Keio University, Tokyo, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acids, Sulfur
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metabolism* Animals Cadmium / pharmacology* Cystathionine beta-Synthase / metabolism Cystathionine gamma-Lyase / metabolism Cysteine / metabolism Glutathione / metabolism Homocysteine / metabolism Hydrogen Sulfide / metabolism Immunohistochemistry Male Rats Rats, Wistar Testis / drug effects*, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids, Sulfur; 454-28-4/Homocysteine; 52-90-4/Cysteine; 70-18-8/Glutathione; 7440-43-9/Cadmium; 7783-06-4/Hydrogen Sulfide; EC 4.2.1.22/Cystathionine beta-Synthase; EC 4.4.1.1/Cystathionine gamma-Lyase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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