Takaaki Akaike

Takaaki Akaike
Tohoku University | Tohokudai · Dept of Moleculr Toxicology

MD PhD

About

399
Publications
34,670
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19,969
Citations
Citations since 2016
115 Research Items
7373 Citations
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201620172018201920202021202202004006008001,0001,200
201620172018201920202021202202004006008001,0001,200
201620172018201920202021202202004006008001,0001,200

Publications

Publications (399)
Article
Full-text available
Anti-oxidative intraocular irrigating solutions (IISs) based on reactive persulfides, such as oxidized glutathione disulfide (GSSG), are commonly used worldwide. However, even with GSSG-based IISs, it has been shown that oxidative stress can occur during surgery, posing a risk to intraocular tissues. This study compared two IISs: one containing GSS...
Article
Full-text available
Reactive sulfur species (RSS) play a role in redox homeostasis; however, adaptive cell responses to excessive intracellular RSS are not well understood. Therefore, in this study, we generated transgenic (Tg) mice overexpressing cystathionine gamma-lyase (CSE) to produce excessive RSS. Contrary to expectations, tissue concentrations of RSS, such as...
Article
Full-text available
Computational fluid dynamics is widely used to simulate droplet-spreading behavior due to respiratory events. However, droplet generation inside the body, such as the number, mass, and particle size distribution, has not been quantitatively analyzed. The aim of this study was to identify quantitative characteristics of droplet generation during cou...
Article
Full-text available
Fluorescent probes are useful tools for the detection of sulfane sulfurs in biological systems. In this work, we report the development of SSP4, a widely used probe generated in our laboratory. We describe its evolution, preparation, and physical/chemical properties. Fluorescence analyses of SSP4 determined its high selectivity and sensitivity to s...
Preprint
Computational fluid dynamics is widely used to simulate droplet-spreading behavior due to respiratory events. However, droplet generation inside the body, such as the number, mass, and particle size distribution, has not been quantitatively analyzed. The aim of this study was to identify quantitative characteristics of droplet generation during cou...
Article
Full-text available
Subtilase cytotoxin (SubAB) is an AB5 toxin mainly produced by the locus of enterocyte effacement-negative Shiga-toxigenic Escherichia coli (STEC) strain such as O113:H21, yet the contribution of SubAB to STEC infectious disease is unclear. We found that SubAB reduced activation of the STEC O113:H21 infection-induced non-canonical NLRP3 inflammasom...
Article
Full-text available
The spike protein of SARS-CoV-2 triggers macrophages and epithelial cells to produce excess levels of pro-inflammatory molecules, which can do more harm than good.
Article
We previously demonstrated different expression patterns of the neuronal nitric oxide synthase (nNOS) splicing variants, nNOS-μ and nNOS-α, in the rat brain; however, their exact functions have not been fully elucidated. In this study, we compared the enzymatic activities of nNOS-μ and nNOS-α and investigated intracellular redox signaling in nNOS-e...
Article
Full-text available
After ligand stimulation, many G protein–coupled receptors (GPCRs) undergo β-arrestin–dependent desensitization, during which they are internalized and either degraded or recycled to the plasma membrane. Some GPCRs are not subject to this type of desensitization because they lack the residues required to interact with β-arrestins. We identified a m...
Article
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Significance Basal-like breast cancers (BLBC) have poor prognosis. Here, we present evidence that reprogrammed transsulfuration is a hallmark of BLBC. Human BLBC tumors exhibit elevated levels of cystathione β-synthetase (CBS) but diminished expressions of oxidative Cys-catabolizing enzymes supporting a Cys-addicted phenotype. We demonstrated that...
Article
Sulfides and persulfides/polysulfides (R-Sn-Rʹ, n > 2; R-Sn-H, n > 1) are endogenously produced metabolites that are abundant in mammalian and human cells and tissues. The most typical persulfides that are widely distributed among different organisms include various reactive persulfides—low-molecular-weight thiol compounds such as cysteine hydroper...
Article
Significance: Polysulfide species (i.e., R-Sn-R', n > 2; R-Sn-H, n > 1) exist in many organisms. Highly nucleophilic nature of hydropersulfides and hydropolysulfides contributes to the potent antioxidant activities of polysulfide species that protect organisms against oxidative and electrophilic stresses. Recent Advances: Accumulating evidence sug...
Article
Full-text available
The mammalian brain is highly vulnerable to oxygen deprivation, yet the mechanism underlying the brain’s sensitivity to hypoxia is incompletely understood. Hypoxia induces accumulation of hydrogen sulfide, a gas that inhibits mitochondrial respiration. Here, we show that, in mice, rats, and naturally hypoxia-tolerant ground squirrels, the sensitivi...
Article
Full-text available
The recent report by Fan et al . alleged that the ProPerDP method is inadequate for the detection of protein persulfidation. Upon careful evaluation of their work, we conclude that the claim made by Fan et al . is not supported by their data, rather founded in methodological shortcomings. It is understood that the ProPerDP method generates a mixtur...
Article
Full-text available
Hydrogen sulfide (H2S) formed during sulfur metabolism in bacteria has been implicated in the development of intrinsic resistance to antibacterial agents. Despite the conversion of H2S to hydropersulfides greatly enhancing the biochemical properties of H2S such as antioxidant activity, the effects of hydropersulfides on antibiotic resistance have r...
Article
The NLRP3 inflammasome is a multiprotein complex responsible for the maturation of precursor forms of interleukin (IL)-1β and IL-18 into active proinflammatory cytokines. Increasing evidence suggests that modulation of redox homeostasis contributes to the activation of the NLRP3 inflammasome. However, specific mechanistic details remain unclear. We...
Article
We investigated the effects of glutathione trisulfide (GSSSG) on lipopolysaccharide (LPS)-induced inflammatory gene expression in immortalized ARPE-19, and primary human and mouse retinal pigment epithelial (RPE) cells. Sulfane sulfur molecules were significantly increased in GSSSG-treated ARPE-19 cells. GSSSG prevented the LPS-induced upregulation...
Article
Aims: Persulfides and other reactive sulfur species are endogenously produced in large amounts in vivo and participate in multiple cellular functions underlying physiological and pathological conditions. In the current study, we aimed to develop an ideal alkylating agent for use in sulfur metabolomics, particularly targeting persulfides and other r...
Article
Full-text available
Cysteine persulfide (CysSSH) and cysteine polysulfides (CysSSnH, n > 1) are cysteine derivatives that have sulfane sulfur atoms bound to cysteine thiol. Advances in analytical methods that detect and quantify persulfides and polysulfides have shown that CysSSH and related species such as glutathione persulfide occur physiologically and are prevalen...
Article
Significance: Redox biology is gaining ground in research related to human physiology (metabolism, signaling), pathophysiology (cancer, cardiovascular disease, neurodegeneration) and toxicology (radiation or xenobiotic-induced damage). A major hurdle in advancing redox medicine is the current lack of understanding the mechanisms underpinning the o...
Article
Cysteine persulfide (CysSSH) and polysulfides (CysS[S] n H, n>1) are cysteine derivatives having sulfane sulfur atoms bound to cysteine thiol. Recent advances in the development of analytical methods for detection and quantification of persulfides and polysulfides have revealed the biological presence, in both prokaryotes and eukaryotes, of persul...
Article
Nitric oxide (NO)-mediated production of cyclic guanosine 3′,5′-monophosphate (cGMP) is a crucial signaling pathway that controls a wide array of neuronal functions, including exocytotic neurotransmitter release. A novel nitrated derivative of cGMP, 8-nitro-cGMP, not only activates cGMP-dependent protein kinase (PKG), but also has membrane permeabi...
Article
Full-text available
Irreversible oxidation of Cys residues to sulfinic/sulfonic forms typically impairs protein function. We found that persulfidation (CysSSH) protects Cys from irreversible oxidative loss of function by the formation of CysSSO 1-3 H derivatives that can subsequently be reduced back to native thiols. Reductive reactivation of oxidized persulfides by t...
Article
Erleuchtend: Eine einzigartige dual-reaktive Fluoreszenzsonde für HSNO wurde entwickelt. Die Sonde zeigt hohe Selektivität und Sensitivität für HSNO in wässrigen Medien und Zellen, was sie zu einem nützlichen Werkzeug zur Aufklärung der biologischen Funktion von HSNO macht. Abstract Thionitrous acid (HSNO), the smallest S-nitrosothiol, is emerging...
Article
Thionitrous acid (HSNO), the smallest S‐nitrosothiol, is emerging as a potential key intermediate in cellular redox regulation linking two signaling molecules H 2 S and NO. However, the chemical biology of HSNO remains poorly understood. A major hurdle is the lack of methods for selective detection of HSNO in biological systems. Here we report the...
Article
Full-text available
Aims: Under hypoxic conditions, nitrite (NO2-) can be reduced to nitric oxide (NO) eliciting vasorelaxation. However, nitrite also exerts vasorelaxant effects of potential therapeutic relevance under normal physiological conditions via undetermined mechanisms. We therefore sought to investigate the mechanism(s) by which nitrite regulates the vascu...
Article
Full-text available
Eukaryotes typically utilize two distinct aminoacyl-tRNA synthetase isoforms, one for cytosolic and one for mitochondrial protein synthesis. However, the genome of budding yeast (Saccharomyces cerevisiae) contains only one cysteinyl-tRNA synthetase gene (YNL247W, also known as CRS1). In this study, we report that CRS1 encodes both cytosolic and mit...
Article
Full-text available
H2S sensors have been well studied; however, H2S scavengers that can attenuate the cellular overproduction of H2S have not been identified. In their Communication (DOI: 10.1002/anie.201905580), M. Xian and co‐workers report a database of H2S sensors, which they used to identify possible H2S scavengers. Potent H2S scavengers (based on the sulfonyl‐a...
Article
H2S‐Sensoren sind gut untersuchte Systeme, allerdings konnten bisher noch keine H2S‐Scavenger identifiziert werden, die die zelluläre Überproduktion von H2S abschwächen. In ihrer Zuschrift (DOI: 10.1002/ange.201905580) beschreiben M. Xian und Mitarbeiter eine Datenbank von H2S‐Sensoren, die zur Identifizierung möglicher H2S‐Scavenger genutzt wurde....
Article
Chronic exposure to methylmercury (MeHg), an environmental electrophilic pollutant, reportedly increases the risk of human cardiac events. We report that exposure to a low, non-neurotoxic dose of MeHg precipitated heart failure induced by pressure overload in mice. Exposure to MeHg at 10 ppm did not induce weight loss typical of higher doses but ca...
Technical Report
Full-text available
Database analysis finds a molecule that could help treat H2S poisoning. Researchers have found a surprising use for a database of fluorescent probes: searching for antidotes to hydrogen sulfide (H2S) poisoning. Washington State University chemist Ming Xian and a team of undergraduate helpers initially built the searchable database to help biologist...
Article
Full-text available
Hydrogen sulfide (H2S) is an important signalling molecule whose up‐ and down‐regulation have specific biological consequences. Although significant advances in H2S up‐regulation, via the development of H2S donors, have been achieved in recent years, precise H2S down‐regulation in biological systems is still challenging. The lack of potent and spec...
Article
Full-text available
Significance This study demonstrates that oxidation of protein kinase G Iα (PKGIα) to its disulfide-activated state occurs in pulmonary arteries during chronic hypoxia, and that this is a protective event that limits progression of pulmonary hypertension by at least two mechanisms. Firstly, it induces pulmonary vasodilation that counters and offset...
Article
Full-text available
Background: Transcription factor Nrf2 (nuclear factor-erythroid 2-related factor 2) plays a key role in detoxification of electrophiles via formation of glutathione (GSH) adducts and subsequent excretion into extracellular spaces. We found that reactive sulfur species (RSS), such as cysteine persulfides produced by cystathionine [Formula: see text...
Article
Background: Asthma-chronic obstructive pulmonary disease overlap (ACO) has frequent exacerbations and a poor quality of life and prognosis compared with those of chronic obstructive pulmonary disease alone. However, the pathogenesis of ACO has not been fully elucidated yet. Objectives: The aim of this study was to investigate nitrosative stress,...
Article
Full-text available
Intracellular polysulfide could regulate the redox balance via its anti-oxidant activity. However, the existence of polysulfide in biological fluids still remains unknown. Recently, we developed a quantitative analytical method for polysulfide and discovered that polysulfide exists in plasma and responds to oxidative stress. In this study, we confi...
Article
Ca ²⁺ /calmodulin (CaM)-dependent protein kinase (CaMK) I is activated by the phosphorylation of a crucial activation loop Thr ¹⁷⁷ by upstream kinases, CaMK kinase (CaMKK), and regulates axonal or dendritic extension and branching. Reactive sulfur species (RSS) modulate protein functions via polysulfidation of the reactive Cys residues. Here, we re...
Article
Cysteine persulfide and cysteine polysulfides are cysteine derivatives having sulfane sulfur atoms bound to cysteine thiol. Accumulating evidence has suggested that cysteine persulfides/polysulfides are abundant in prokaryotes and eukaryotes and play important roles in diverse biological processes such as antioxidant host defense and redox-dependen...
Article
We previously reported that 8-nitroguanosine 3′,5′-cyclic monophosphate (8-nitro-cGMP) is endogenously produced via nitric oxide/reactive oxygen species signaling pathways and it reacts with protein thiol residues to add cGMP structure to proteins through S-guanylation. S-Guanylation occurs on synaptosomal-associated protein 25 (SNAP-25), which is...
Article
Hydropersulfides and related polysulfides have recently become topics of significant interest due to their physiological prevalence and proposed biological functions. Currently, examination of the effects of hydropersulfide treatment on cells has been difficult due to their lack of inherent stability with respect to disproportionation. Herein, it i...
Article
Full-text available
The physiological importance of reactive sulfur species (RSS) such as cysteine hydropersulfide (CysSSH) has been increasingly recognized in recent years. We have established a reactive sulfur metabolomics analysis by using RSS metabolic profiling, which revealed appreciable amounts of RSS generated endogenously and ubiquitously in both prokaryotic...
Chapter
8-Nitroguanosine 3′,5′-cyclic monophosphate (8-nitro-cGMP), which is the second messenger in nitric oxide/reactive oxygen species redox signaling, covalently binds to protein thiol groups (called S-guanylation) and exerts various biological functions. Synaptosomal associated protein 25 (SNAP-25), a member of soluble N-ethylmaleimide-sensitive facto...
Article
Defective mitochondrial dynamics through aberrant interactions between mitochondria and actin cytoskeleton is increasingly recognized as a key determinant of cardiac fragility after myocardial infarction (MI). Dynamin-related protein 1 (Drp1), a mitochondrial fission–accelerating factor, is activated locally at the fission site through interactions...
Article
Full-text available
Defective mitochondrial dynamics through aberrant interactions between mitochondria and actin cytoskeleton is increasingly recognized as a key determinant of cardiac fragility after myocardial infarction (MI). Dynamin-related protein 1 (Drp1), a mitochondrial fission–accelerating factor, is activated locally at the fission site through interactions...
Article
Osteocytes regulate bone remodeling, especially in response to mechanical loading and unloading of bone, with nitric oxide reported to play an important role in that process. In the present study, we found that 8-nitroguanosine 3′,5′-cyclic monophosphate (8-nitro-cGMP), a second messenger of nitric oxide in various types of cells, was produced by o...
Article
NLRP3 inflammasome is an intracellular protein complex, which is responsible for the maturation of precursor forms of interleukin (IL)-1β and IL-18 into active proinflammatory cytokines and initiation of pyroptotic cell death. Although generation of reactive oxygen species (ROS) has been implicated in the activation of NLRP3 inflammasome, detail me...
Article
Sulfide quinone reductase (SQR) protein is a mitochondrial enzyme highly conserved among species and has been considered as an important enzyme mediating proton transfer in mitochondria during sulfur metabolism (respiration), however, the detailed mechanism and physiological impacts of SQR function are still unknown. We generated SQR genome-edited...
Article
Reactive persulfides such as cysteine persulfide and glutathione persulfide are produced by bacteria including Salmonella during sulfur metabolism. The biological significance of bacterial reactive persulfides in host-pathogen interactions still warrants investigation. We found that reactive persulfides produced by Salmonella Typhimurium LT2 regula...
Article
Cysteine persulfide and polysulfide produced in cells exist in abundance in both low-molecular -weight and protein fractions. They can act as an antioxidant and thus protect cells from harmful free radicals and oxidative stress that may cause various diseases. However, how these reactive sulfur molecules are formed, or what role they play exactly w...
Conference Paper
KEAP1-NRF2 system is a sulfur-employing defense mechanism. NRF2-mediated activation of the cytoprotective genes substantially mediates chemoprevention of cancers. Recent studies described that NRF2 activation in tumor microenvironment is also beneficial resulting in the potentiation of anticancer immunity. In contrast to these bright sides of NRF2...
Article
Full-text available
The chemical biology of thiols (RSH, e.g., cysteine and cysteine containing proteins/peptides) has been a topic of extreme interest for many decades due to their reported roles in protein structure/folding, redox signaling, metal ligation, cellular protection and enzymology. While many of the studies on thiol/sulfur biochemistry have focused on thi...
Article
Cysteine persulfide and polysulfide are produced in cells and exist in abundance in both low‐molecular‐weight and protein fractions. However, the mechanism of regulation of the formation of cellular cysteine polysulfides and the physiological functions of cysteine persulfides/polysulfides produced in cells are not fully understood. We recently demo...