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The findings were published in the online version of Scientific Reports on November 9.Glutathione, an antioxidant with antidotal properties, plays an important role in keeping us healthy. This finding could contribute to the development of new ways to prevent, diagnose and treat various oxidative stress-related conditions including Alzheimer’s, aging, cancer, lifestyle-related diseases, hardened arteries, and organ damage caused by medicines and toxins.The team was led by Kobe University Graduate School of Medicine, Division of Evidence-Based Laboratory Medicine Assistant Professor IRINO Yasuhiro and Associate Professor TOH Ryuji, in collaboration with Professor HIRATA Ken-ichi (Kobe University, Division of Cardiovascular Medicine) and Professor MIYATA Okiko (Kobe Pharmaceutical University, Medicinal Chemistry Laboratory)Glutathione is a major antioxidant component within cells, and keeps our bodies healthy by contributing to the detoxification of foreign substances. Monitoring glutathione metabolism in the body can help with early diagnosis of illness, as glutathione is consumed when bodies experience oxidative stress. However, glutathione concentration in the blood is 100- to 1000-fold lower than levels within cells, making it hard to accurately measure. Our bodies also compensate for the depletion of glutathione under stress, so circulating levels will not necessarily decrease during illness. This makes it difficult to accurately monitor the metabolism of glutathione just by measuring its levels in the blood.Increasing levels of glutathione in the body could help to prevent and treat a variety of conditions which involve oxidative stress and organ damage caused by toxins. However, simply ingesting glutathione does not efficiently increase glutathione levels in the body.2-aminobutyric acid (2-AB) has been reported as a basic component of ophthalmic acid, which is produced when glutathione is synthesized. Until now, the metabolism and physiological effects of 2-AB itself were unknown. The group investigated whether 2-AB could be a marker for glutathione dynamics, and whether it could be used to modulate glutathione homeostasis.Searching for leads to develop new diagnoses and treatment to combat heart failure, the group started by comprehensively analyzing metabolites in the bloodstreams of atrial septal defect patients using a gas chromatography mass spectrometer. Results showed that levels of 2-AB were higher in these patients than in healthy subjects, and 2-AB levels decreased after the closure of atrial septal defect. Then, the group clarified for the first time that 2-AB is a byproduct of cysteine, one of the constituent amino acids of glutathione (figure 1), and revealed that activation of glutathione synthetic pathway under oxidative damage led to 2-AB accumulation. Because blood concentration of 2-AB reflects the metabolism of glutathione within the body, 2-AB could potentially be used as a new biomarker for early detection of oxidative stress.Intriguingly, the group also found that 2-AB promotes glutathione synthesis. The anticancer drug doxorubicin causes heart damage via oxidative stress as an adverse effect. They discovered that when taken orally, 2-AB increases the concentration of glutathione in the bloodstream and the heart, lessening the heart damage caused by doxorubicin (figure 2).This research found that as well as being a biomarker, 2-AB itself is an antioxidant that can be used to effectively increase glutathione in the body (patent pending). 2-AB is a naturally-occurring amino acid that can be found in everyday food products. Future research will examine which foods contain high levels of 2-AB, the recommended level to ingest, whether it can be used as an antioxidant for other organs, and the development of medicines and functional food for clinical use.Journal informationTitle“2-Aminobutyric acid modulates glutathione homeostasis in the myocardium”DOI10.1038/srep36749AuthorsYasuhiro Irino1,2, Ryuji Toh1, Manabu Nagao3, Takeshige Mori3, Tomoyuki Honjo3, Masakazu Shinohara2,4, Shigeyasu Tsuda3, Hideto Nakajima3, Seimi Satomi-Kobayashi3, Toshiro Shinke3, Hidekazu Tanaka3, Tatsuro Ishida3, Okiko Miyata5, and Ken-ichi Hirata1, 31 Division of Evidence-Based Laboratory Medicine, Kobe University Graduate School of Medicine2 The Integrated Center for Mass Spectrometry, Kobe University School of Medicine3 Division of Cardiovascular Medicine, Kobe University Schood 4 Division of Epidemiology, Kobe University School of Medicine5 Medicinal Chemistry Laboratory, Kobe Pharmaceutical UniversityJournalScientific ReportsResearchersIRINO YasuhiroGraduate School of MedicineToh RyujiAssociate ProfessorGraduate School of MedicineHirata KenichiProfessorGraduate School of MedicineNagao ManabuAssistant ProfessorGraduate School of MedicineShinohara MasakazuProfessorGraduate School of MedicineHideto NakajimaGraduate School of MedicineKobayashi SeimiAssociate ProfessorHospitalShinke ToshirouHospitalTanaka HidekazuAssociate ProfessorHospitalIshida TatsurouProfessorGraduate School of Health SciencesGraduate School of MedicineSHAREMore from these researchersPress releases2022.05.09Medicine, dentistry and pharmacologyRevealing the individual immune cells inside the plaque that causes life-threatening heart attacksPress releases2021.04.21Medicine, dentistry and pharmacologyNewly developed AI uses combination of ECG and X-ray results to diagnose arrhythmic disordersPress releases2020.05.22Medicine, dentistry and pharmacologyMechanism underlying the development of diabetes and fatty liver illuminatedPress releases2017.07.10Medicine, dentistry and pharmacologyA novel practical test for the function of HDL, the carrier of “good” cholesterolMore about these topicsPress releases2024.02.16Medicine, dentistry and pharmacologySelf-monitoring improves physical activity of care-needing elderlyPress releases2021.01.18Medicine, dentistry and pharmacologyFGF23 hormone from red blood cell precursors promotes hematopoietic stem cell mobilizationPress releases2018.11.12Medicine, dentistry and pharmacologyLack of exercise impacts mental health in Japanese expatsPress releases2022.12.06Social sciencesSchool children who meet movement guidelines report better healthページの先頭へ1-1, Rokkodai-cho, Nada-ku, Kobe, 657-8501, JAPANProspective studentsCurrent studentsAlumsCorporate and societyFaculty and staffContactAccessJobsOfficial social media accountsCampus calendarPrivacy policySite policySite map© Kobe University