Tags

Type your tag names separated by a space and hit enter

Taurine treatment prevents derangement of the hepatic γ-glutamyl cycle and methylglyoxal metabolism in a mouse model of classical homocystinuria: regulatory crosstalk between thiol and sulfinic acid metabolism.
FASEB J 2018; 32(3):1265-1280FJ

Abstract

Cystathionine β-synthase-deficient homocystinuria (HCU) is a poorly understood, life-threatening inborn error of sulfur metabolism. Analysis of hepatic glutathione (GSH) metabolism in a mouse model of HCU demonstrated significant depletion of cysteine, GSH, and GSH disulfide independent of the block in trans-sulfuration compared with wild-type controls. HCU induced the expression of the catalytic and regulatory subunits of γ-glutamyl ligase, GSH synthase (GS), γ-glutamyl transpeptidase 1, 5-oxoprolinase (OPLAH), and the GSH-dependent methylglyoxal detoxification enzyme, glyoxalase-1. Multiple components of the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated antioxidant-response regulatory axis were induced without any detectable activation of Nrf2. Metabolomic analysis revealed the accumulation of multiple γ-glutamyl amino acids and that plasma ophthalmate levels could serve as a noninvasive marker for hepatic redox stress. Neither cysteine, nor betaine treatment was able to reverse the observed enzyme inductions. Taurine treatment normalized the expression levels of γ-glutamyl ligase C/M, GS, OPLAH, and glyoxalase-1, and reversed HCU-induced deficits in protein glutathionylation by acting to double GSH levels relative to controls. Collectively, our data indicate that the perturbation of the γ-glutamyl cycle could contribute to multiple sequelae in HCU and that taurine has significant therapeutic potential for both HCU and other diseases for which GSH depletion is a critical pathogenic factor.-Maclean, K. N., Jiang, H., Aivazidis, S., Kim, E., Shearn, C. T., Harris, P. S., Petersen, D. R., Allen, R. H., Stabler, S. P., Roede, J. R. Taurine treatment prevents derangement of the hepatic γ-glutamyl cycle and methylglyoxal metabolism in a mouse model of classical homocystinuria: regulatory crosstalk between thiol and sulfinic acid metabolism.

Authors+Show Affiliations

Department of Pediatrics, University of Colorado Health Sciences Center, Aurora, Colorado, USA.Department of Pediatrics, University of Colorado Health Sciences Center, Aurora, Colorado, USA.Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Aurora, Colorado, USA.Department of Pediatrics, University of Colorado Health Sciences Center, Aurora, Colorado, USA.Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Aurora, Colorado, USA.Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Aurora, Colorado, USA.Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Aurora, Colorado, USA.Department of Medicine, University of Colorado Health Sciences Center, Aurora, Colorado, USA.Department of Medicine, University of Colorado Health Sciences Center, Aurora, Colorado, USA.Department of Pharmaceutical Sciences, University of Colorado Health Sciences Center, Aurora, Colorado, USA.

Pub Type(s)

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

Language

eng

PubMed ID

29101223

Citation

Maclean, Kenneth N., et al. "Taurine Treatment Prevents Derangement of the Hepatic Γ-glutamyl Cycle and Methylglyoxal Metabolism in a Mouse Model of Classical Homocystinuria: Regulatory Crosstalk Between Thiol and Sulfinic Acid Metabolism." FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, vol. 32, no. 3, 2018, pp. 1265-1280.
Maclean KN, Jiang H, Aivazidis S, et al. Taurine treatment prevents derangement of the hepatic γ-glutamyl cycle and methylglyoxal metabolism in a mouse model of classical homocystinuria: regulatory crosstalk between thiol and sulfinic acid metabolism. FASEB J. 2018;32(3):1265-1280.
Maclean, K. N., Jiang, H., Aivazidis, S., Kim, E., Shearn, C. T., Harris, P. S., ... Roede, J. R. (2018). Taurine treatment prevents derangement of the hepatic γ-glutamyl cycle and methylglyoxal metabolism in a mouse model of classical homocystinuria: regulatory crosstalk between thiol and sulfinic acid metabolism. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 32(3), pp. 1265-1280. doi:10.1096/fj.201700586R.
Maclean KN, et al. Taurine Treatment Prevents Derangement of the Hepatic Γ-glutamyl Cycle and Methylglyoxal Metabolism in a Mouse Model of Classical Homocystinuria: Regulatory Crosstalk Between Thiol and Sulfinic Acid Metabolism. FASEB J. 2018;32(3):1265-1280. PubMed PMID: 29101223.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Taurine treatment prevents derangement of the hepatic γ-glutamyl cycle and methylglyoxal metabolism in a mouse model of classical homocystinuria: regulatory crosstalk between thiol and sulfinic acid metabolism. AU - Maclean,Kenneth N, AU - Jiang,Hua, AU - Aivazidis,Stefanos, AU - Kim,Eugene, AU - Shearn,Colin T, AU - Harris,Peter S, AU - Petersen,Dennis R, AU - Allen,Robert H, AU - Stabler,Sally P, AU - Roede,James R, Y1 - 2018/01/03/ PY - 2017/11/5/pubmed PY - 2018/11/15/medline PY - 2017/11/5/entrez KW - cystathionine KW - glutathione KW - ophthalmate KW - β-synthase SP - 1265 EP - 1280 JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JO - FASEB J. VL - 32 IS - 3 N2 - Cystathionine β-synthase-deficient homocystinuria (HCU) is a poorly understood, life-threatening inborn error of sulfur metabolism. Analysis of hepatic glutathione (GSH) metabolism in a mouse model of HCU demonstrated significant depletion of cysteine, GSH, and GSH disulfide independent of the block in trans-sulfuration compared with wild-type controls. HCU induced the expression of the catalytic and regulatory subunits of γ-glutamyl ligase, GSH synthase (GS), γ-glutamyl transpeptidase 1, 5-oxoprolinase (OPLAH), and the GSH-dependent methylglyoxal detoxification enzyme, glyoxalase-1. Multiple components of the transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated antioxidant-response regulatory axis were induced without any detectable activation of Nrf2. Metabolomic analysis revealed the accumulation of multiple γ-glutamyl amino acids and that plasma ophthalmate levels could serve as a noninvasive marker for hepatic redox stress. Neither cysteine, nor betaine treatment was able to reverse the observed enzyme inductions. Taurine treatment normalized the expression levels of γ-glutamyl ligase C/M, GS, OPLAH, and glyoxalase-1, and reversed HCU-induced deficits in protein glutathionylation by acting to double GSH levels relative to controls. Collectively, our data indicate that the perturbation of the γ-glutamyl cycle could contribute to multiple sequelae in HCU and that taurine has significant therapeutic potential for both HCU and other diseases for which GSH depletion is a critical pathogenic factor.-Maclean, K. N., Jiang, H., Aivazidis, S., Kim, E., Shearn, C. T., Harris, P. S., Petersen, D. R., Allen, R. H., Stabler, S. P., Roede, J. R. Taurine treatment prevents derangement of the hepatic γ-glutamyl cycle and methylglyoxal metabolism in a mouse model of classical homocystinuria: regulatory crosstalk between thiol and sulfinic acid metabolism. SN - 1530-6860 UR - https://www.unboundmedicine.com/medline/citation/29101223/Taurine_treatment_prevents_derangement_of_the_hepatic_γ_glutamyl_cycle_and_methylglyoxal_metabolism_in_a_mouse_model_of_classical_homocystinuria:_regulatory_crosstalk_between_thiol_and_sulfinic_acid_metabolism_ L2 - http://www.fasebj.org/doi/full/10.1096/fj.201700586R?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -