Polyamines regulate cell growth and cellular methylglyoxal in high‐glucose medium independently of intracellular glutathione

Abstract

Edited by Miguel De la RosaPolyamines can presumably inhibit protein glycation, when associated with the methylglyoxal inevitably produced during glycolysis. Herein, we hypothesized a nonenzymatic interaction between putrescine and methylglyoxal in putrescine-deficient or -overexpressing Dictyostelium cells in high-glucose medium, which can control methylglyoxal production. Putrescine was essentially required for growth rescue accompanying methylglyoxal detoxification when cells underwent growth defect and cell cycle G1-arrest when supplemented with high glucose. Furthermore, methylglyoxal regulation by putrescine seemed to be a parallel pathway independent of the changes in cellular glutathione content in high-glucose medium. Consequently, we suggest that Dictyostelium cells need polyamines for normal growth and cellular methylglyoxal regulation.Keywords: Dictyostelium discoideum; glutathione; methylglyoxal; polyamines; putrescine High amounts of cellular glucose, a simple aldosic monosaccharide and a reducing sugar, can cause cellular damage that is followed by increased production of chemically reactive MG in mammals [1]. Glucose has been elucidated as a major a-dicarbonyl compound causing AGEs to form and furthermore is associated with engagement of their cellular RAGE in diabetic complications [2]. Particularly, MG has been strongly suggested to activate nonenzymatic glycation of proteins to form irreversible AGEs [3,4]. Although the biochemical origins of MG production have still not been addressed distinctly [5], MG seems to alter the intracellular content of both GSH and ROS in eukaryotes [6].To explain the biochemical roles of MG and its regulating enzymes, many types of enzyme systems have been proposed in mammals [7,8]. In microorganisms, our current study revealed that cellular MG levels altered Candida cell physiology and differentiation through their MG-consuming enzyme systems [9,10]. Additionally, we previously reported the crucial effect of MG on cell growth, cell cycle, and differentiation when MG-reducing aldose reductase (AlrA) is regulated in Dictyostelium [11]. However, nonenzymatic MG-scavenging molecules have not been sufficiently studied either in vitro or in vivo. The limited cellular MG regulation by MG-consuming enzymes is not sufficient for the nonenzymatic MG production,

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

“…, glyoxal, MG, phenylglyoxal) and H 2 O 2 than to reference strains [ 12 ]. These previous reports concur with our previous findings that demonstrated MG production by GSH deprivation and/or exogenous glucose treatment in the growth media resulted in growth defects with G1 phase-specific cell-cycle arrest in D. dictyostelium alrA and ornithine decarboxylase disruptants [ 50 , 51 ]. Because the main experimental materials were constructed based on Δgcs1 to accumulate cellular MG and pyruvate, this study excluded GSH-supplemented Δgcs1 to emphasize the Mgd and Mgr activities in MK603 ( Δmgd1 / Δgcs1 , MK703 ( Δadh1 / Δgcs1 ), and MK803 ( Δmgd1 / Δadh1 / Δgcs1 ).…”