A key role for mitochondria in endothelial signaling by plasma cysteine/cystine redox potential |
| |
| Authors: | Young-Mi Go Heonyong Park Michael Koval Michael Orr Matthew Reed Yongliang Liang Debra Smith Jan Pohl Dean P Jones |
| |
| Institution: | 1. Division of Pulmonary Medicine, Emory University, Atlanta, GA 30322, USA;2. Department of Molecular Biology, Dankook University, Yongin, Korea;3. Microchemical and Proteomics Facility, Department of Medicine, Emory University, Atlanta, GA 30322, USA;4. Biotechnology Core Facility, DSR, Center for Disease Control and Prevention, Atlanta, GA 30333, USA;1. Shaanxi Key Laboratory of Industrial Automation, Shaanxi Sci-Tech University, Hanzhong 723001, China;2. School of Mechanical Engineering, Shaanxi Sci-Tech University, Hanzhong 723001, China;3. Electronic Materials Research Laboratory, Key Laboratory of the Ministry of Education & International Center for Dielectric Research, Xi’an Jiaotong University, Xi’an 710049, China;1. Department of Physics, Coimbatore Institute of Technology, Coimbatore, India;2. Department of Engineering, University College of Bergen, Norway;3. Department of Physics, PSG College of Technology, Coimbatore, India;4. Department of Chemistry, College of Science, Yeungnam University, South Korea;1. Department of Pharmacology, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA, USA;2. Department of Neurology, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA, USA;3. Departments of Radiology and Neurosurgery, Milton S. Hershey Medical Center, and Kinesiology, Pennsylvania State University, Hershey, PA, USA |
| |
| Abstract: | The redox potential of the plasma cysteine/cystine couple (EhCySS) is oxidized in association with risk factors for cardiovascular disease (CVD), including age, smoking, type 2 diabetes, obesity, and alcohol abuse. Previous in vitro findings support a cause–effect relationship for extracellular EhCySS in cell signaling pathways associated with CVD, including those controlling monocyte adhesion to endothelial cells. In this study, we provide evidence that mitochondria are a major source of reactive oxygen species (ROS) in the signaling response to a more oxidized extracellular EhCySS. This increase in ROS was blocked by overexpression of mitochondrial thioredoxin-2 (Trx2) in endothelial cells from Trx2-transgenic mice, suggesting that mitochondrial thiol antioxidant status plays a key role in this redox signaling mechanism. Mass spectrometry-based redox proteomics showed that several classes of plasma membrane and cytoskeletal proteins involved in inflammation responded to this redox switch, including vascular cell adhesion molecule, integrins, actin, and several Ras family GTPases. Together, the data show that the proinflammatory effects of oxidized plasma EhCySS are due to a mitochondrial signaling pathway that is mediated through redox control of downstream effector proteins. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
