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http://dx.doi.org/10.4014/jmb.2010.10057

Methylglyoxal-Scavenging Enzyme Activities Trigger Erythroascorbate Peroxidase and Cytochrome c Peroxidase in Glutathione-Depleted Candida albicans  

Kang, Sa-Ouk (Laboratory of Biophysics, School of Biological Sciences, and Institute of Microbiology, Seoul National University)
Kwak, Min-Kyu (Department of Food and Nutrition, Institute of Food and Nutrition Science, Eulji University)
Publication Information
Journal of Microbiology and Biotechnology / v.31, no.1, 2021 , pp. 79-91 More about this Journal
Abstract
γ-Glutamylcysteine synthetase (Gcs1) and glutathione reductase (Glr1) activity maintains minimal levels of cellular methylglyoxal in Candida albicans. In glutathione-depleted Δgcs1, we previously saw that NAD(H)-linked methylglyoxal oxidoreductase (Mgd1) and alcohol dehydrogenase (Adh1) are the most active methylglyoxal scavengers. With methylglyoxal accumulation, disruptants lacking MGD1 or ADH1 exhibit a poor redox state. However, there is little convincing evidence for a reciprocal relationship between methylglyoxal scavenger genes-disrupted mutants and changes in glutathione-(in)dependent redox regulation. Herein, we attempt to demonstrate a functional role for methylglyoxal scavengers, modeled on a triple disruptant (Δmgd1/Δadh1/Δgcs1), to link between antioxidative enzyme activities and their metabolites in glutathione-depleted conditions. Despite seeing elevated methylglyoxal in all of the disruptants, the result saw a decrease in pyruvate content in Δmgd1/Δadh1/Δgcs1 which was not observed in double gene-disrupted strains such as Δmgd1/Δgcs1 and Δadh1/Δgcs1. Interestingly, Δmgd1/Δadh1/Δgcs1 exhibited a significantly decrease in H2O2 and superoxide which was also unobserved in Δmgd1/Δgcs1 and Δadh1/Δgcs1. The activities of the antioxidative enzymes erythroascorbate peroxidase and cytochrome c peroxidase were noticeably higher in Δmgd1/Δadh1/Δgcs1 than in the other disruptants. Meanwhile, Glr1 activity severely diminished in Δmgd1/Δadh1/Δgcs1. Monitoring complementary gene transcripts between double gene-disrupted Δmgd1/Δgcs1 and Δadh1/Δgcs1 supported the concept of an unbalanced redox state independent of the Glr1 activity for Δmgd1/Δadh1/Δgcs1. Our data demonstrate the reciprocal use of Eapx1 and Ccp1 in the absence of both methylglyoxal scavengers; that being pivotal for viability in non-filamentous budding yeast.
Keywords
Alcohol dehydrogenase 1; Candida albicans; erythroascorbate peroxidase; glutathione; methylglyoxal; NAD(H)-linked methylglyoxal oxidoreductase;
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1 de Mendez I, Young KRJ, Bignon J, Lambre CR. 1991. Biochemical characteristics of alveolar macrophage-specific peroxidase activities in the rat. Arch. Biochem. Biophys. 289: 319-323.   DOI
2 Park S-J, Kwak M-K, Kang S-O. 2017. Schiff bases of putrescine with methylglyoxal protect from cellular damage caused by accumulation of methylglyoxal and reactive oxygen species in Dictyostelium discoideum. Int. J. Biochem. Cell Biol. 86: 54-66.   DOI
3 Ku M, Baek Y-U, Kwak M-K, Kang S-O. 2017. Candida albicans glutathione reductase downregulates Efg1-mediated cyclic AMP/protein kinase A pathway and leads to defective hyphal growth and virulence upon decreased cellular methylglyoxal content accompanied by activating alcohol dehydrogenase and glycolytic enzymes. Biochim. Biophys. Acta Gen. Subj. 1861: 772-788.   DOI
4 Ayer A, Tan SX, Grant CM, Meyer AJ, Dawes IW, Perrone GG. 2010. The critical role of glutathione in maintenance of the mitochondrial genome. Free Radic. Biol. Med. 49: 1956-1968.   DOI
5 Kim J-S, Seo J-H, Kang S-O. 2014. Glutathione initiates the development of Dictyostelium discoideum through the regulation of YakA. Biochim. Biophys. Acta 1843: 664-674.   DOI
6 Huh W-K, Song Y-B, Lee Y-S, Ha C-W, Kim S-T, Kang S-O. 2008. D-Erythroascorbic acid activates cyanide-resistant respiration in Candida albicans. Biochem. Biophys. Res. Commun. 369: 401-406.   DOI
7 Huh W-K, Kim S-T, Kim H, Jeong G, Kang S-O. 2001. Deficiency of D-erythroascorbic acid attenuates hyphal growth and virulence of Candida albicans. Infect. Immun. 69: 3939-3946.   DOI
8 Rizhsky L, Hallak-Herr E, Van Breusegem F, Rachmilevitch S, Barr JE, Rodermel S, et al. 2002. Double antisense plants lacking ascorbate peroxidase and catalase are less sensitive to oxidative stress than single antisense plants lacking ascorbate peroxidase or catalase. Plant J. 32: 329-342.   DOI
9 Penning TM. 2015. The aldo-keto reductases (AKRs): overview. Chem. Biol. Interact. 234: 236-246.   DOI
10 Hagen TM, Aw TY, Jones DP. 1988. Glutathione uptake and protection against oxidative injury in isolated kidney cells. Kidney Int. 34: 74-81.   DOI
11 Izawa S, Inoue Y, Kimura A. 1995. Oxidative stress response in yeast: effect of glutathione on adaptation to hydrogen peroxide stress in Saccharomyces cerevisiae. FEBS Lett. 368: 73-76.   DOI
12 Kim B-J, Choi C-H, Lee C-H, Jeong S-Y, Kim J-S, Kim B-Y, et al. 2005. Glutathione is required for growth and prespore cell differentiation in Dictyostelium. Dev. Biol. 284: 387-398.   DOI
13 Choi C-H, Park S-J, Jeong S-Y, Yim H-S, S.-O. K. 2008. Methylglyoxal accumulation by glutathione dpletion leads to cell cycle arrest in Dictyostelium. Mol. Microbiol. 70: 1293-1304.   DOI
14 Kwak MK, Lee MH, Park SJ, Shin SM, Liu R, Kang SO. 2016. Polyamines regulate cell growth and cellular methylglyoxal in highglucose medium independently of intracellular glutathione. FEBS Lett. 590: 739-749.   DOI
15 Ciriolo MR, Palamara AT, Incerpi S, Lafavia E, Bue MC, De Vito P, et al. 1997. Loss of GSH, oxidative stress, and decrease of intracellular pH as sequential steps in viral infection. J. Biol. Chem. 272: 2700-2708.   DOI
16 Saikusa T, Rhee H-i, Watanabe K, Murata K, Kimura A. 1987. Metabolism of 2-oxoaldehydes in bacteria: purification and characterization of methylglyoxal reductase from Escherichia coli. Agric. Biol. Chem. 51: 1893-1899.   DOI
17 de Arriba SG, Stuchbury G, Yarin J, Burnell J, Loske C, Munch G. 2007. Methylglyoxal impairs glucose metabolism and leads to energy depletion in neuronal cells--protection by carbonyl scavengers. Neurobiol. Aging 28: 1044-1050.   DOI
18 Wu C, Amrani N, Jacobson A, Sachs MS. 2007. Translation initiation: extract systems and molecular genetics. 429: 203-225
19 Garay-Arroyo A, Covarrubias AA. 1999. Three genes whose expression is induced by stress in Saccharomyces cerevisiae. Yeast 15: 879-892.   DOI
20 Khan A, Ahmad A, Ahmad Khan L, Padoa CJ, van Vuuren S, Manzoor N. 2015. Effect of two monoterpene phenols on antioxidant defense system in Candida albicans. Microb. Pathog. 80: 50-56.   DOI
21 Jiang H, English AM. 2006. Phenotypic analysis of the ccp1Delta and ccp1Delta-ccp1W191F mutant strains of Saccharomyces cerevisiae indicates that cytochrome c peroxidase functions in oxidative-stress signaling. J. Inorg. Biochem. 100: 1996-2008.   DOI
22 Ashraf M. 2009. Biotechnological approach of improving plant salt tolerance using antioxidants as markers. Biotechnol. Adv. 27: 84-93.   DOI
23 Kwak M-K, Song S-H, Ku M, Kang S-O. 2015. Candida albicans erythroascorbate peroxidase regulates intracellular methylglyoxal and reactive oxygen species independently of D-erythroascorbic acid. FEBS Lett. 89: 1863-1871.
24 Hwang C-S, Baek Y-U, Yim H-S, Kang S-O. 2003. Protective roles of mitochondrial manganese-containing superoxide dismutase against various stresses in Candida albicans. Yeast 20: 929-941.   DOI
25 Spickett CM, Smirnoff N, Pitt AR. 2000. The biosynthesis of erythroascorbate in Saccharomyces cerevisiae and its role as an antioxidant. Free Radic. Biol. Med. 28: 183-192.   DOI
26 Kitajima S. 2008. Hydrogen peroxide-mediated inactivation of two chloroplastic peroxidases, ascorbate peroxidase and 2-cys peroxiredoxin. Photochem. Photobiol. 84: 1404-1409.   DOI
27 Pócsi I, Prade RA, Penninckx MJ. 2004. Glutathione, altruistic metabolite in fungi. Adv. Microb. Physiol. 49: 1-76.   DOI
28 Banerjee D, Koll A, Filarowski A, Bhattacharyya SP, Mukherjee S. 2004. Interaction between methyl glyoxal and ascorbic acid: experimental and theoretical aspects. Spectrochim. Acta A Mol. Biomol. Spectrosc. 60: 1523-1526.   DOI
29 Thornalley PJ, Langborg A, Minhas HS. 1999. Formation of glyoxal, methylglyoxal and 3-deoxyglucosone in the glycation of proteins by glucose. Biochem. J. 344: 109-116.   DOI
30 Thornalley PJ. 2008. Protein and nucleotide damage by glyoxal and methylglyoxal in physiological systems - role in ageing and disease. Drug Metabol. Drug Interact. 23: 125-150.   DOI
31 Baek Y-U, Kim Y-R, Yim H-S, Kang S-O. 2004. Disruption of gamma-glutamylcysteine synthetase results in absolute glutathione auxotrophy and apoptosis in Candida albicans. FEBS Lett. 556: 47-52.   DOI
32 Yonetani T, Ray GS. 1966. Studies on cytochrome c peroxidase.3. Kinetics of the peroxidatic oxidation of ferrocytochrome c catalyzed by cytochrome c peroxidase. J. Biol. Chem. 241: 700-706.   DOI
33 Matthis AL, Erman JE. 1995. Cytochrome c peroxidase-catalyzed oxidation of yeast iso-1 ferrocytochrome c by hydrogen peroxide. Ionic strength dependence of the steady-state parameters. Biochemistry 34: 9985-9990.   DOI
34 Ku, M., Baek Y-U, Kwak M-K, Kang S-O. 2017. Candida albicans glutathione reductase downregulates Efg1-mediated cyclic AMP/protein kinase A pathway and leads to defective hyphal growth and virulence upon decreased cellular methylglyoxal content accompanied by activating alcohol dehydrogenase and glycolytic enzymes. Biochim. Biophys. Acta 1861: 772-788.   DOI
35 Kwak MK, Song SH, Ku M, Kang SO. 2015. Candida albicans erythroascorbate peroxidase regulates intracellular methylglyoxal and reactive oxygen species independently of D-erythroascorbic acid. FEBS Lett. 589: 1863-1871.   DOI
36 Shin Y, Lee S, Ku M, Kwak M-K, Kang S-O. 2017. Cytochrome c peroxidase regulates intracellular reactive oxygen species and methylglyoxal via enzyme activities of erythroascorbate peroxidase and glutathione-related enzymes in Candida albicans. Int. J. Biochem. Cell Biol. 92: 183-201.   DOI
37 Sherman F. 2002. Getting started with yeast. Methods Enzymol. 350: 3-41.   DOI
38 Feng Q, Summers E, Guo B, Fink G. 1999. Ras signaling is required for serum-induced hyphal differentiation in Candida albicans. J. Bacteriol. 181: 6339-6346.   DOI
39 Hwang C-S, Oh J-H, Huh W-K, Yim H-S, Kang S-O. 2003. Ssn6, an important factor of morphological conversion and virulence in Candida albicans. Mol. Microbiol. 47: 1029-1043.   DOI
40 Fonzi WA, Irwin MY. 1993. Isogenic strain construction and gene mapping in Candida albicans. Genetics 134: 717-728.   DOI
41 Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193: 265-275.   DOI
42 Ramasamy R, Yan SF, Schmidt AM. 2012. Advanced glycation endproducts: from precursors to RAGE: round and round we go. Amino Acids 42: 1151-1161.   DOI
43 Pailla K, Blonde-Cynober F, Aussel C, De Bandt JP, Cynober L. 2000. Branched-chain keto-acids and pyruvate in blood: measurement by HPLC with fluorimetric detection and changes in older subjects. Clin. Chem. 46: 848-853.   DOI
44 Biswas S, Ray M, Misra S, Dutta DP, Ray S. 1997. Selective inhibition of mitochondrial respiration and glycolysis in human leukaemic leucocytes by methylglyoxal. Biochem. J. 323: 343-348.   DOI
45 Huh W-K, Lee B-H, Kim S-T, Kim Y-R, Rhie G-E, Baek Y-W, et al. 1998. D-Erythroascorbic acid is an important antioxidant molecule in Saccharomyces cerevisiae. Mol. Microbiol. 30: 895-903.   DOI
46 Pogolotti ALJ, Santi DV. 1982. High-pressure liquid chromatography--ultraviolet analysis of intracellular nucleotides. Anal. Biochem. 126: 335-345.   DOI
47 Newton GL, Fahey RC. 1995. Determination of biothiols by bromobimane labeling and high-performance liquid chromatography. Methods Enzymol. 251: 148-166.   DOI
48 Benov L, Sztejnberg L, Fridovich I. 1998. Critical evaluation ofthe use of hydroethidine as a measure of superoxide anionradical. Free Radic. Biol. Med. 25: 826-831.   DOI
49 Carlberg I, Mannervik B. 1985. Glutathione reductase. Methods Enzymol. 113: 484-490.   DOI
50 Nakano Y, Asada K. 1987. Purification of ascorbate peroxidase in spinach chloroplasts; its inactivation in ascorbate-depleted medium and reactivation by monodehydroascorbate radical. Plant Cell Physiol. 28: 131-140.
51 Yim H-S, Kang S-O, Hah Y-C, Chock PB, Yim MB. 1995. Free radicals generated during the glycation reaction of amino acids by methylglyoxal. A model study of protein-cross-linked free radicals. J. Biol. Chem. 270: 28228-28233.   DOI
52 Szent-Gyorgyi A, Együd LG, McLaughlin JA. 1967. Keto-aldehydes and cell division. Science 155: 539-541.   DOI
53 Lee C, Yim MB, Chock PB, Yim H-S, Kang S-O. 1998. Oxidation-reduction properties of methylglyoxal-modified protein in relation to free radical generation. J. Biol. Chem. 273: 25272-25278.   DOI
54 Szent-Gyorgyi A, McLaughlin JA. 1975. Interaction of glyoxal and methylglyoxal with biogenic amines. Proc. Natl. Acad. Sci. USA 72: 1610-1611.   DOI
55 Song F, Schmidt AM. 2012. Glycation and insulin resistance: novel mechanisms and unique targets? Arterioscler. Thromb. Vasc. Biol. 32: 1760-1765.   DOI
56 Kang Y, Edwards LG, Thornalley PJ. 1996. Effect of methylglyoxal on human leukaemia 60 cell growth: modification of DNA G1 growth arrest and induction of apoptosis. Leuk. Res. 20: 397-405.   DOI
57 Takatsume Y, Izawa S, Inoue Y. 2006. Methylglyoxal as a signal initiator for activation of the stress-activated protein kinase cascade in the fission yeast Schizosaccharomyces pombe. J. Biol. Chem. 281: 9086-9092.   DOI
58 Choi C-H, Park S-J, Jeong S-Y, Yim H-S, Kang S-O. 2008. Methylglyoxal accumulation by glutathione depletion leads to cell cycle arrest in Dictyostelium. Mol. Microbiol. 70: 1293-1304.   DOI
59 Kwak M-K, Ku M, Kang S-O. 2014. NAD+-linked alcohol dehydrogenase 1 regulates methylglyoxal concentration in Candida albicans. FEBS Lett. 588: 1144-1153.   DOI
60 Vander Jagt DL, Hunsaker LA. 2003. Methylglyoxal metabolism and diabetic complications: roles of aldose reductase, glyoxalase-I, betaine aldehyde dehydrogenase and 2-oxoaldehyde dehydrogenase. Chem. Biol. Interact. 143-144: 341-351.   DOI
61 Kwak M-K, Ku M, Kang S-O. 2018. Inducible NAD (H)-linked methylglyoxal oxidoreductase regulates cellular methylglyoxal and pyruvate through enhanced activities of alcohol dehydrogenase and methylglyoxal-oxidizing enzymes in glutathione-depleted Candida albicans. Biochim. Biophys. Acta 1862: 18-39.   DOI
62 Aguirre J, Rios-Momberg M, Hewitt D, Hansberg W. 2005. Reactive oxygen species and development in microbial eukaryotes. Trends Microbiol. 13: 111-118.   DOI
63 Yu S, Qin W, Zhuang G, Zhang X, Chen G, Liu W. 2009. Monitoring oxidative stress and DNA damage induced by heavy metals in yeast expressing a redox-sensitive green fluorescent protein. Curr. Microbiol. 58: 504-510.   DOI
64 Emri T, Pocsi I, Szentirmai A. 1997. Glutathione metabolism and protection against oxidative stress caused by peroxides in Penicillium chrysogenum. Free Radic. Biol. Med. 23: 809-814.   DOI
65 Westwater J, McLaren NF, Dormer UH, Jamieson DJ. 2002. The adaptive response of Saccharomyces cerevisiae to mercury exposure. Yeast 19: 233-239.   DOI
66 Dantas Ada S, Day A, Ikeh M, Kos I, Achan B, Quinn J. 2015. Oxidative stress responses in the human fungal pathogen, Candida albicans. Biomolecules 5: 142-165.   DOI