Cadmium exposure alters metabolomics of sulfur-containing amino acids in rat testes

Yasoo Sugiura, Misato Kashiba, Kayo Maruyama, Koichi Hoshikawa, Ryoko Sasaki, Kazuyoshi Saito, Hideo Kimura, Nobuhito Goda, Makoto Suematsu

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Abstract

This study aimed to examine distribution of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), the hydrogen sulfide (H 2S)-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 H2S 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.

Original languageEnglish
Pages (from-to)781-787
Number of pages7
JournalAntioxidants and Redox Signaling
Volume7
Issue number5-6
DOIs
Publication statusPublished - 2005 May

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Cystathionine
Sulfur Amino Acids
Metabolomics
Cadmium
Sulfur
Lyases
Testis
Rats
Glutathione Disulfide
Amino Acids
Cysteine
Sertoli Cells
Germ Cells
Cells
S-Adenosylhomocysteine
Cadmium Chloride
S-Adenosylmethionine
Hydrogen Sulfide
Spermatogonia
Metabolome

ASJC Scopus subject areas

  • Biochemistry

Cite this

Sugiura, Y., Kashiba, M., Maruyama, K., Hoshikawa, K., Sasaki, R., Saito, K., ... Suematsu, M. (2005). Cadmium exposure alters metabolomics of sulfur-containing amino acids in rat testes. Antioxidants and Redox Signaling, 7(5-6), 781-787. https://doi.org/10.1089/ars.2005.7.781

Cadmium exposure alters metabolomics of sulfur-containing amino acids in rat testes. / Sugiura, Yasoo; Kashiba, Misato; Maruyama, Kayo; Hoshikawa, Koichi; Sasaki, Ryoko; Saito, Kazuyoshi; Kimura, Hideo; Goda, Nobuhito; Suematsu, Makoto.

In: Antioxidants and Redox Signaling, Vol. 7, No. 5-6, 05.2005, p. 781-787.

Research output: Contribution to journalArticle

Sugiura, Y, Kashiba, M, Maruyama, K, Hoshikawa, K, Sasaki, R, Saito, K, Kimura, H, Goda, N & Suematsu, M 2005, 'Cadmium exposure alters metabolomics of sulfur-containing amino acids in rat testes', Antioxidants and Redox Signaling, vol. 7, no. 5-6, pp. 781-787. https://doi.org/10.1089/ars.2005.7.781
Sugiura, Yasoo ; Kashiba, Misato ; Maruyama, Kayo ; Hoshikawa, Koichi ; Sasaki, Ryoko ; Saito, Kazuyoshi ; Kimura, Hideo ; Goda, Nobuhito ; Suematsu, Makoto. / Cadmium exposure alters metabolomics of sulfur-containing amino acids in rat testes. In: Antioxidants and Redox Signaling. 2005 ; Vol. 7, No. 5-6. pp. 781-787.
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