A5100767586- Amino Acid Enzymes and Metabolism
- Neuroscience and Neuropharmacology Research
- Biomedical Research and Pathophysiology
- Sulfur Compounds in Biology
- Drug Transport and Resistance Mechanisms
- Epigenetics and DNA Methylation
- Neuroinflammation and Neurodegeneration Mechanisms
- Heme Oxygenase-1 and Carbon Monoxide
- Tryptophan and brain disorders
- Ferroptosis and cancer prognosis
- Vitamin C and Antioxidants Research
- Folate and B Vitamins Research
- Metabolism and Genetic Disorders
- Endoplasmic Reticulum Stress and Disease
- Gastric Cancer Management and Outcomes
- Receptor Mechanisms and Signaling
- Genomics, phytochemicals, and oxidative stress
- Antioxidant Activity and Oxidative Stress
- RNA modifications and cancer
- Stress Responses and Cortisol
- Redox biology and oxidative stress
- Immune Response and Inflammation
- Esophageal Cancer Research and Treatment
- Phytochemicals and Antioxidant Activities
- Glutathione Transferases and Polymorphisms
Niigata University
2015-2024
Saitama Medical University
2020
Niigata University of Pharmacy and Medical and Life Sciences
2019
Showa University
2017
Yamagata University
2006-2016
Yamagata University Hospital
2008-2015
Iwate University
2012-2015
Niigata Cancer Center Hospital
2015
Kyoto University
2011
Keio University
2011
Electrophiles and reactive oxygen species have been implicated in the pathogenesis of many diseases. Transcription factor Nrf2 was recently identified as a general regulator one defense mechanism against such havoc. regulates inducible expression group detoxication enzymes, glutathione S-transferase NAD(P)H:quinone oxidoreductase, via antioxidant response elements. Using peritoneal macrophages from Nrf2-deficient mice, we show here that also controls electrophile- oxidative stress-inducible...
In mammalian cultured cells, the cystine/glutamate exchange transport mediated by system x(c)- is important to maintain intracellular GSH levels. System consists of two protein components, xCT and heavy chain 4F2 antigen. The activity induced various stimuli, including electrophilic agents like diethyl maleate. present study, we have investigated mechanism transcriptional regulation mRNA gene consisted twelve exons sequence analysis identified four electrophile response element (EpRE)-like...
Cystine/glutamate transporter, designated as system x(-)(c), mediates cystine entry in exchange for intracellular glutamate mammalian cells. This transporter consists of two protein components, xCT and 4F2 heavy chain, the former is predicted to mediate transport activity. plays a pivotal role maintaining GSH levels extracellular cystine/cysteine redox balance cultured To clarify physiological roles this vivo, we generated characterized mice lacking xCT. The xCT(-/-) were healthy appearance...
Abstract System x c − was recently described as the most upstream node in a novel form of regulated necrotic cell death, called ferroptosis. In this context, small molecule erastin reported to target and inhibit system , leading cysteine starvation, glutathione depletion consequently ferroptotic death. Although inhibitory effect towards is well-documented, nothing known about its mechanism action. Therefore, we sought interrogate more detail underlying erastin’s pro-ferroptotic effects. When...
Abstract Sorafenib, a protein kinase inhibitor approved for the treatment of hepatocellular carcinoma and advanced renal cell carcinoma, has been repeatedly reported to induce ferroptosis by possibly involving inhibition cystine/glutamate antiporter, known as system x c − . Using combination well-defined genetically engineered tumor lines canonical small molecule inhibitors, we now provide unequivocal evidence that sorafenib does not in series unlike cognate inhibitors sulfasalazine erastin....
GSH is the major antioxidant and detoxifier of xenobiotics in mammalian cells. A strong decrease intracellular has been frequently linked to pathological conditions like ischemia/reperfusion injury degenerative diseases including diabetes, atherosclerosis, neurodegeneration. Although essential for survival, deleterious effects deficiency can often be compensated by thiol-containing antioxidants. Using three genetically defined cellular systems, we show here that forced expression xCT,...
Exposure of mouse peritoneal macrophages to oxidative and sulfhydryl-reactive agents in vitro enhances synthesis a few cellular proteins that may be important self-defense system. A cDNA encoding novel stress-inducible protein, designated MSP23 (macrophage 23-kDa stress protein), was cloned from library the by differential screening. 1.0-kilobase mRNA transcript hybridized with gradually increased upon culture vitro. Treatment diethylmaleate or glucose/glucose oxidase, which generates H2O2,...
The ubiquitin-proteasome pathway degrades ubiquitinated proteins to remove damaged or misfolded protein and thus plays an important role in the maintenance of many cellular processes. Because is also crucial for tumor cell growth survival, proteasome inhibition by specific inhibitors exhibits potent antitumor effects cancer cells. xCT, a subunit cystine antiporter system xc (-), cysteine glutathione homeostasis. Several recent reports have revealed that xCT involved survival; however, it was...
System x c − exchanges intracellular glutamate for extracellular cystine, giving it a potential role in glutathione synthesis and nonvesicular release. We report that mice lacking the specific xCT subunit of system ( −/− ) do not have lower hippocampal content, increased oxidative stress or brain atrophy, nor exacerbated spatial reference memory deficits with aging. Together these results indicate loss does induce vivo . Young did however display working deficit. Interestingly, we observed...
Amyotrophic lateral sclerosis is the most common adult-onset motor neuron disease and evidence from mice expressing amyotrophic sclerosis-causing SOD1 mutations suggest that neurodegeneration a non-cell autonomous process where microglial cells influence progression. However, microglial-derived neurotoxic factors still remain largely unidentified in sclerosis. With excitotoxicity being major mechanism proposed to cause death sclerosis, our hypothesis was excessive glutamate release by...
Transport system xc− is a member of plasma membrane heterodimeric amino-acid transporters and consists two protein components, xCT 4F2hc. This mediates cystine entry coupled with the exodus intracellular glutamate regulates glutathione (GSH) levels in most mammalian cultured cells. We studied activity GSH content human ovarian cancer cell line (A2780) its cisplatin (CDDP)-resistant variant (A2780DDP). The rate uptake was approximately 4.5-fold higher A2780DDP cells than A2780 mediated by...
Transport of system xc¯ is an exchange agency with high specificity for anionic form cystine and glutamate. The protein mediating this transport a disulfide-linked heterodimer light chain named xCT heavy previously known as 4F2hc. We have isolated two cDNAs encoding from the human cDNA library. One clone coded 501 amino acids 12 putative transmembrane domains. When functionally expressed in Xenopus oocytes together 4F2hc, induced activity whose characteristics are similar to those xc¯....
Mammalian cells express a transport system known as x<sub>c</sub><sup>−</sup>, which is an exchange agency specific for anionic forms of cystine and glutamate. System x<sub>c</sub><sup>−</sup> activity important to maintain both intracellular glutathione levels the redox balance between cysteine in extracellular milieu. We have shown that cloned cDNAs encoding transporter consist two components, xCT heavy chain 4F2 antigen. In present study, we investigated mRNA distribution these components...
The effects of a pumpkin paste concentrate and its components on oral glucose tolerance serum lipid levels were determined in non-obese type 2 diabetic Goto-Kakizaki (GK) rats. In the test, concentrate-fed group maintained lower level than control between 15 60 min. compounds considered to be effective improving contained methanol extract relatively abundant amounts isolated identified as trigonelline (TRG) nicotinic acid (NA).
Malfunctioning of system xc–, responsible for exchanging intracellular glutamate extracellular cystine, can cause oxidative stress and excitotoxicity, both important phenomena in the pathogenesis Parkinson's disease (PD). We used mice lacking xCT (xCT_/_ mice), specific subunit xc˜, to investigate involvement this antiporter PD. Although cystine that is imported via xc˜ reduced cysteine, rate-limiting substrate synthesis glutathione, deletion did not result decreased glutathione levels...
Abstract The transport activity for cystine in cultured human fibroblasts decreased after incubation of the cells under a low oxygen concentration. After 48 h 3% oxygen, Vmax was to less than one-third that control cells, with little change Km. similar observed 10-40 days several times passages. When these oxygen-cultured were incubated room air, enhanced lag about 4 and almost completely restored within 24 h. This restoration required protein synthesis. increased by 50% exposure hyperoxia...
Abstract The cystine‐glutamate exchanger (xCT) promotes glutathione synthesis by catalyzing cystine uptake and glutamate release. released may modulate normal neural signaling contribute to excitotoxicity in pathological situations. Uncertainty, however, remains as neither the expression levels nor distribution of xCT have been unambiguously determined. In fact, has reported astrocytes, neurons, oligodendrocytes microglia, but most information derives from cell cultures. Here, we show...
The cystine/glutamate antiporter, system xc- , is essential for the efficient uptake of cystine into cells. Interest in mechanisms function soared with recognition that presents most upstream node ferroptosis, a recently described form regulated necrosis relevant degenerative diseases and cancer. Since targeting hold great potential to efficiently combat tumor growth metastasis certain tumors, we disrupted substrate-specific subunit xCT (SLC7A11) highly metastatic mouse B16F10 melanoma cell...
The excessive inflammatory response of macrophages plays a vital role in the pathogenesis various diseases. dynamic metabolic alterations macrophages, including amino acid metabolism, are known to orchestrate their phenotype. To explore new pathway that regulates response, we examined metabolome changes mouse peritoneal (PMs) lipopolysaccharide (LPS) and found coordinated increase cysteine its related metabolites, suggesting an enhanced demand for during response. Because Slc7a11, which...