Protein cysteine S-nitrosylation provides reducing power by enhancing lactate dehydrogenase activity in Trichomonas vagi
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RESEARCH
Protein cysteine S‑nitrosylation provides reducing power by enhancing lactate dehydrogenase activity in Trichomonas vaginalis under iron deficiency Wei‑Hung Cheng1†, Kuo‑Yang Huang2†, Seow‑Chin Ong1, Fu‑Man Ku1, Po‑Jung Huang3,4, Chi‑Ching Lee4,5, Yuan‑Ming Yeh4, Rose Lin1, Cheng‑Hsun Chiu6 and Petrus Tang1,6*
Abstract Background: Iron plays essential roles in the pathogenesis and proliferation of Trichomonas vaginalis, the causative agent of the most prevalent non-viral human sexually transmitted infection. We previously demonstrated that under iron deficiency, the endogenous nitric oxide (NO) is accumulated and capable of regulating the survival of T. vaginalis. Herein, we aim to explore the influence of NO on the activity of the pyruvate-reducing enzyme lactate dehydroge‑ nase in T. vaginalis (TvLDH). Methods: Levels of lactate and pyruvate were detected for determining glycolysis activity in T. vaginalis under iron deficiency. Quantitative PCR was performed to determine the expression of TvLDH. S-nitrosylated (SNO) proteomics was conducted to identify the NO-modified proteins. The activities of glyceraldehyde-3-phosphate dehydrogenase (TvGAPDH) and TvLDH were measured after sodium nitrate treatment. The effects of protein nitrosylation on the pro‑ duction of cellular reducing power were examined by measuring the amount of nicotinamide adenine dinucleotide (NAD) and the ratio of the NAD redox pair (NAD+/NADH). Results: We found that although the glycolytic pathway was activated in cells under iron depletion, the level of pyruvate was decreased due to the increased level of TvLDH. By analyzing the SNO proteome of T. vaginalis upon iron deficiency, we found that TvLDH is one of the glycolytic enzymes modified by SNO. The production of pyruvate was significantly reduced after nitrate treatment, indicating that protein nitrosylation accelerated the consumption of pyruvate by increasing TvLDH activity. Nitrate treatment also induced NAD oxidation, suggesting that protein nitros‑ ylation was the key posttranslational modification controlling cellular redox status. Conclusions: We demonstrated that NO-mediated protein nitrosylation plays pivotal roles in the regulation of glyco‑ lysis, pyruvate metabolism, and the activity of TvLDH. The recycling of oxidized NAD catalyzed by TvLDH provided the reducing power that allowed T. vaginalis to adapt to the iron-deficient environment. Keywords: Trichomonas vaginalis, Iron deficiency, Glycolysis, Cysteine S-nitrosylation, Lactate dehydrogenase, Nicotinamide adenine dinucleotide
*Correspondence: [email protected] † Wei-Hung Cheng and Kuo-Yang Huang contributed equally to this work 1 Department of Parasitology, College of Medicine, Chang Gung University, Guishan District, Taoyuan City, Taiwan Full list of author information is available at the end of the article © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution a
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