I have been working on oxidative stress and redox signaling in Vascular Biology Section in Chobanian and Avedisian School of Medicine. My current and previous projects are as follows.
– Glutaredoxin and ischemic limb vascularization. In recent years my focus is the roles of glutaredoxin-1 (Glrx) in cardiovascular disease. Glrx regulates cellular signaling and transcription by reversing protein-glutathione adducts. This relatively unexplored enzyme and its targets and function have just emerged as a significant redox signaling mechanism. We identified Glrx as an anti-angiogenic molecule which may suppress hypoxia inducible factor (HIF)-1a activation. We aim to to develop therapeutic strategy to improve poor ischemic limb vascularization in diabetes and aged individuals.
– Tumor angiogenesis: we found mouse melanoma implants growth does not correlate with endothelial angiogenesis in endothelial-specific Glrx transgenic mice. We are developing a new area of Glrx and tumor angiogenesis.
– We also explore Glrx role in liver fibrosis with my collaborators. Glrx-deficient mice develop fatty liver and diet-induced liver fibrosis. Glrx inhibits angiogenesis as well as fibrotic process. Our collaborative paper shows Glrx attenuates lung fibrosis. We aim to examine the Glrx effects on liver fibrosis models.
– In the past, I worked on vascular complications in glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD is a key enzyme of the pentose phosphate pathway which contributes to NADPH generation. G6PD deficiency is the most prevalent enzymopathy in humans, and was thought to worsen cardiovascular disease due to oxidative stress and hemolytic anemia. However, we found that angiotensin II –induced cardiovascular hypertrophy was attenuated in G6PD-deficient mice. There are many enzymes that depend on NADPH including the oxidant source, NADPH oxidase, and enzymes in the cholesterol synthesis pathway. We also demonstrated higher blood pressure, less atherosclerosis, lower oxidants and plasma cholesterol in G6PD-deficient mice with apoE-/- background. These studies are actually consistent with clinical reports on G6PD-deficient people, and confirmed a contribution of NADPH oxidase to vascular hypertrophy and atherosclerosis.
Overall, based on my broad clinical experiences in internal medicine, I would like to develop my research to bring benefit to patients.
- Member, Whitaker Cardiovascular Institute, Boston University
- Boston Medical Center
- Kanazawa University, MD
- Published on 4/28/2022
Tsukahara Y, Ferran B, Minetti ET, Chong BSH, Gower AC, Bachschmid MM, Matsui R. Administration of Glutaredoxin-1 Attenuates Liver Fibrosis Caused by Aging and Non-Alcoholic Steatohepatitis. Antioxidants (Basel). 2022 Apr 28; 11(5). PMID: 35624731.
- Published on 7/28/2021
Mustafa Rizvi SH, Shao D, Tsukahara Y, Pimentel DR, Weisbrod RM, Hamburg NM, McComb ME, Matsui R, Bachschmid MM. Oxidized GAPDH transfers S-glutathionylation to a nuclear protein Sirtuin-1 leading to apoptosis. Free Radic Biol Med. 2021 10; 174:73-83. PMID: 34332079.
- Published on 9/16/2020
Burns M, Rizvi SHM, Tsukahara Y, Pimentel DR, Luptak I, Hamburg NM, Matsui R, Bachschmid MM. Role of Glutaredoxin-1 and Glutathionylation in Cardiovascular Diseases. Int J Mol Sci. 2020 Sep 16; 21(18). PMID: 32948023.
- Published on 3/5/2020
Watanabe Y, Watanabe K, Fujioka D, Nakamura K, Nakamura T, Uematsu M, Bachschmid MM, Matsui R, Kugiyama K. Protein S-glutathionylation stimulate adipogenesis by stabilizing C/EBPß in 3T3L1 cells. FASEB J. 2020 04; 34(4):5827-5837. PMID: 32141127.
- Published on 2/14/2020
Matsui R, Hamburg NM. Eating Chocolate to Improve Muscle Health and Walking Ability in Patients With Peripheral Artery Disease. Circ Res. 2020 02 28; 126(5):600-602. PMID: 32078440.
- Published on 1/23/2020
Matsui R, Ferran B, Oh A, Croteau D, Shao D, Han J, Pimentel DR, Bachschmid MM. Redox Regulation via Glutaredoxin-1 and Protein S-Glutathionylation. Antioxid Redox Signal. 2020 04 01; 32(10):677-700. PMID: 31813265.
- Published on 10/26/2019
Yura Y, Chong BSH, Johnson RD, Watanabe Y, Tsukahara Y, Ferran B, Murdoch CE, Behring JB, McComb ME, Costello CE, Janssen-Heininger YMW, Cohen RA, Bachschmid MM, Matsui R. Endothelial cell-specific redox gene modulation inhibits angiogenesis but promotes B16F0 tumor growth in mice. FASEB J. 2019 12; 33(12):14147-14158. PMID: 31647879.
- Published on 9/19/2019
Kimura T, Ferran B, Tsukahara Y, Shang Q, Desai S, Fedoce A, Pimentel DR, Luptak I, Adachi T, Ido Y, Matsui R, Bachschmid MM. Production of adeno-associated virus vectors for in vitro and in vivo applications. Sci Rep. 2019 09 19; 9(1):13601. PMID: 31537820.
- Published on 3/5/2019
Shao D, Yao C, Kim MH, Fry J, Cohen RA, Costello CE, Matsui R, Seta F, McComb ME, Bachschmid MM. Improved mass spectrometry-based activity assay reveals oxidative and metabolic stress as sirtuin-1 regulators. Redox Biol. 2019 04; 22:101150. PMID: 30877853.
- Published on 1/25/2019
Weinberg EO, Ferran B, Tsukahara Y, Hatch MMS, Han J, Murdoch CE, Matsui R. IL-33 induction and signaling are controlled by glutaredoxin-1 in mouse macrophages. PLoS One. 2019; 14(1):e0210827. PMID: 30682073.
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