A key role for mitochondria in endothelial signaling by plasma cysteine/cystine redox potential. Export

@article{citeulike:6076359, abstract = {The redox potential (E(h)) of the plasma cysteine/cystine (Cys/CySS) couple (E(h)CySS) is oxidized in association with risk factors for cardiovascular disease (CVD), including age, smoking, type II diabetes, obesity, and alcohol abuse. Previous in vitro findings support a cause-effect relationship of extracellular E(h)CySS in cell signaling pathways associated with CVD, including those controlling monocyte adhesion to endothelial cells. In the present study, we provide evidence that mitochondria are a major source of reactive oxygen species (ROS) in the signaling response to a more oxidized extracellular E(h)CySS. 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 pro-inflammatory effects of oxidized plasma E(h)CySS are due to a mitochondrial signaling pathway which is mediated through redox control of downstream effector proteins.}, author = {Go, Young-Mi M. and Park, Heonyong and Koval, Michael and Orr, Michael and Reed, Matthew and Liang, Yongliang and Smith, Debra and Pohl, Jan and Jones, Dean P.}, citeulike-article-id = {6076359}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.freeradbiomed.2009.10.050}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S0891584909006959}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19879942}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19879942}, day = {29}, doi = {10.1016/j.freeradbiomed.2009.10.050}, issn = {1873-4596}, journal = {Free radical biology \& medicine}, month = {October}, posted-at = {2009-11-07 00:23:18}, priority = {3}, title = {A key role for mitochondria in endothelial signaling by plasma cysteine/cystine redox potential.}, url = {http://dx.doi.org/10.1016/j.freeradbiomed.2009.10.050}, year = {2009} }

TY - JOUR ID - citeulike:6076359 L3 - citeulike-article-id:6076359 N2 - The redox potential (E(h)) of the plasma cysteine/cystine (Cys/CySS) couple (E(h)CySS) is oxidized in association with risk factors for cardiovascular disease (CVD), including age, smoking, type II diabetes, obesity, and alcohol abuse. Previous in vitro findings support a cause-effect relationship of extracellular E(h)CySS in cell signaling pathways associated with CVD, including those controlling monocyte adhesion to endothelial cells. In the present study, we provide evidence that mitochondria are a major source of reactive oxygen species (ROS) in the signaling response to a more oxidized extracellular E(h)CySS. 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 pro-inflammatory effects of oxidized plasma E(h)CySS are due to a mitochondrial signaling pathway which is mediated through redox control of downstream effector proteins. JF - Free radical biology & medicine SN - 1873-4596 TI - A key role for mitochondria in endothelial signaling by plasma cysteine/cystine redox potential. AU - Go, Young-Mi AU - Park, Heonyong AU - Koval, Michael AU - Orr, Michael AU - Reed, Matthew AU - Liang, Yongliang AU - Smith, Debra AU - Pohl, Jan AU - Jones, Dean PY - 2009/10/29/ UR - http://dx.doi.org/10.1016/j.freeradbiomed.2009.10.050 ER -