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Homocysteine- and cysteine-mediated growth defect is not associated with induction of oxidative stress response genes in yeast.
Biochem J. 2006 May 15; 396(1):61-9.BJ

Abstract

Intracellular thiols like cysteine, homocysteine and glutathione play a critical role in the regulation of important cellular processes. Alteration of intracellular thiol concentration results in many diseased states; for instance, elevated levels of homocysteine are considered to be an independent risk factor for cardiovascular disease. Yeast has proved to be an excellent model system for studying many human diseases since it carries homologues of nearly 40% of human disease genes and many fundamental pathways are highly conserved between the two organisms. In the present study, we demonstrate that cysteine and homocysteine, but not glutathione, inhibit yeast growth in a concentration-dependent manner. Using deletion strains (str2Delta and str4Delta) we show that cysteine and homocysteine independently inhibit yeast growth. Transcriptional profiling of yeast treated with cysteine and homocysteine revealed that genes coding for antioxidant enzymes like glutathione peroxidase, catalase and superoxide dismutase were down-regulated. Furthermore, transcriptional response to homocysteine did not show any similarity to the response to H2O2. We also failed to detect induction of reactive oxygen species in homocysteine- and cysteine-treated cells, using fluorogenic probes. These results indicate that homocysteine- and cysteine-induced growth defect is not due to the oxidative stress. However, we found an increase in the expression of KAR2 (karyogamy 2) gene, a well-known marker of ER (endoplasmic reticulum) stress and also observed HAC1 cleavage in homocysteine- and cysteinetreated cells, which indicates that homocysteine- and cysteine-mediated growth defect may probably be attributed to ER stress. Transcriptional profiling also revealed that genes involved in one-carbon metabolism, glycolysis and serine biosynthesis were up-regulated on exogenous addition of cysteine and homocysteine, suggesting that cells try to reduce the intracellular concentration of thiols by up-regulating the genes involved in their metabolism.

Authors+Show Affiliations

Institute of Genomics and Integrative Biology, Mall Road, Delhi-110007, India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16433631

Citation

Kumar, Arun, et al. "Homocysteine- and Cysteine-mediated Growth Defect Is Not Associated With Induction of Oxidative Stress Response Genes in Yeast." The Biochemical Journal, vol. 396, no. 1, 2006, pp. 61-9.
Kumar A, John L, Alam MM, et al. Homocysteine- and cysteine-mediated growth defect is not associated with induction of oxidative stress response genes in yeast. Biochem J. 2006;396(1):61-9.
Kumar, A., John, L., Alam, M. M., Gupta, A., Sharma, G., Pillai, B., & Sengupta, S. (2006). Homocysteine- and cysteine-mediated growth defect is not associated with induction of oxidative stress response genes in yeast. The Biochemical Journal, 396(1), 61-9.
Kumar A, et al. Homocysteine- and Cysteine-mediated Growth Defect Is Not Associated With Induction of Oxidative Stress Response Genes in Yeast. Biochem J. 2006 May 15;396(1):61-9. PubMed PMID: 16433631.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Homocysteine- and cysteine-mediated growth defect is not associated with induction of oxidative stress response genes in yeast. AU - Kumar,Arun, AU - John,Lijo, AU - Alam,Md Mahmood, AU - Gupta,Ankit, AU - Sharma,Gayatri, AU - Pillai,Beena, AU - Sengupta,Shantanu, PY - 2006/1/26/pubmed PY - 2006/6/1/medline PY - 2006/1/26/entrez SP - 61 EP - 9 JF - The Biochemical journal JO - Biochem J VL - 396 IS - 1 N2 - Intracellular thiols like cysteine, homocysteine and glutathione play a critical role in the regulation of important cellular processes. Alteration of intracellular thiol concentration results in many diseased states; for instance, elevated levels of homocysteine are considered to be an independent risk factor for cardiovascular disease. Yeast has proved to be an excellent model system for studying many human diseases since it carries homologues of nearly 40% of human disease genes and many fundamental pathways are highly conserved between the two organisms. In the present study, we demonstrate that cysteine and homocysteine, but not glutathione, inhibit yeast growth in a concentration-dependent manner. Using deletion strains (str2Delta and str4Delta) we show that cysteine and homocysteine independently inhibit yeast growth. Transcriptional profiling of yeast treated with cysteine and homocysteine revealed that genes coding for antioxidant enzymes like glutathione peroxidase, catalase and superoxide dismutase were down-regulated. Furthermore, transcriptional response to homocysteine did not show any similarity to the response to H2O2. We also failed to detect induction of reactive oxygen species in homocysteine- and cysteine-treated cells, using fluorogenic probes. These results indicate that homocysteine- and cysteine-induced growth defect is not due to the oxidative stress. However, we found an increase in the expression of KAR2 (karyogamy 2) gene, a well-known marker of ER (endoplasmic reticulum) stress and also observed HAC1 cleavage in homocysteine- and cysteinetreated cells, which indicates that homocysteine- and cysteine-mediated growth defect may probably be attributed to ER stress. Transcriptional profiling also revealed that genes involved in one-carbon metabolism, glycolysis and serine biosynthesis were up-regulated on exogenous addition of cysteine and homocysteine, suggesting that cells try to reduce the intracellular concentration of thiols by up-regulating the genes involved in their metabolism. SN - 1470-8728 UR - https://www.unboundmedicine.com/medline/citation/16433631/Homocysteine__and_cysteine_mediated_growth_defect_is_not_associated_with_induction_of_oxidative_stress_response_genes_in_yeast_ L2 - https://portlandpress.com/biochemj/article-lookup/doi/10.1042/BJ20051411 DB - PRIME DP - Unbound Medicine ER -