Evidence for peroxynitrite as a signaling molecule in flow-dependent activation of c-Jun NH2-terminal kinase

1999 ◽  
Vol 277 (4) ◽  
pp. H1647-H1653 ◽  
Author(s):  
Young-Mi Go ◽  
Rakesh P. Patel ◽  
Matthew C. Maland ◽  
Heonyong Park ◽  
Joseph S. Beckman ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Protein Kinase ◽  
Reactive Nitrogen Species ◽  
Mitogen Activated Protein Kinase ◽  
Reactive Nitrogen ◽  
Tyrosine Nitration ◽  
Nitrogen Species ◽  
Laminar Shear Stress ◽  
As Stress

The c-Jun NH2-terminal kinase (JNK), also known as stress-activated protein kinase, is a mitogen-activated protein kinase that determines cell survival in response to environmental stress. Activation of JNK involves redox-sensitive mechanisms and physiological stimuli such as shear stress, the dragging force generated by blood flow over the endothelium. Laminar shear stress has antiatherogenic properties and controls structure and function of endothelial cells by mechanisms including production of nitric oxide (NO) and superoxide ([Formula: see text]). Here we show that both NO and [Formula: see text] are required for activation of JNK by shear stress in endothelial cells. The present study also demonstrates that exposure of endothelial cells to shear stress increases tyrosine nitration, a marker of reactive nitrogen species formation. Furthermore, inhibitors or scavengers of NO, [Formula: see text], or reactive nitrogen species prevented shear-dependent increase in tyrosine nitration and activation of JNK. Peroxynitrite alone, added to cells as a bolus or generated over 60 min by 3-morpholinosydnonimine, also activates JNK. These results suggest that reactive nitrogen species, in this case most likely peroxynitrite, act as signaling molecules in the mechanoactivation of JNK.

The effect of aliphatic, naphthenic, and aromatic hydrocarbons on production of reactive oxygen species and reactive nitrogen species in rat brain synaptosome fraction: the involvement of calcium, nitric oxide synthase, mitochondria, and phospholipase A11Abbreviations: BIM, bisindolylmaleimide; [Ca2+]i, concentration of intracellular calcium; ChAT, cholin acetyltransferase; CSA, cyclosporin A; DCF, 2′,7′-dichlorofluorescein; H2DCF-DA, 2′,7′-dichlorodihydrofluorescin diacetate; DEDA, dimethyleicosadienoic acid; ERK, extracellular signal-regulated kinases; Fura-2 AM, 5-oxazolecarboxylic acid, 2-(6-(bis(2-((acetyloxy)methoxy)-2-oxoethyl)amino)-5-(2-(bis(2-((acetyloxy)methoxy)-2oxoethyl)amino)-5-methylphenoxy)ethoxy)-2-benzofuranyl)-, (acetyloxy) methyl ester; GABA-T, gamma-aminobutyric acid transaminase; HBSS, Hanks’ balanced salt solution; La3+, lanthanum; MAPK, mitogen-activated protein kinase; MeHg, methyl mercury; MEK, extracellular signal-regulated protein kinase; MeOH, methanol; MTP, mitochondrial permeability transition pore; L-NAME, Nω-nitro-l-arginine methyl ester; NO·, nitrogen oxide; NOS, NO· synthase; O2·−, superoxide; PLA2, phospholipase A2; PKC, protein kinase C; RNS, reactive nitrogen species; ROS, reactive oxygen species; SOD, superoxide dismutase; TMB, 1,2,4-trimethylbenzene; TMCH, 1,2,4-trimethylcyclohexane; and U73122, 1-(6-[17beta-3-methoxyestra- 1,3,5(10)-trien- 17-yl]-aminohexyl)- 1H-pyrrole-2,5-dione.

2001 ◽  
Vol 62 (1) ◽  
pp. 119-128 ◽  
Author(s):  
Oddvar Myhre ◽  
Frode Fonnum
Keyword(s):  
Reactive Oxygen Species ◽  
Protein Kinase ◽  
Methyl Ester ◽  
Reactive Nitrogen Species ◽  
Reactive Oxygen ◽  
Mitogen Activated Protein Kinase ◽  
Reactive Nitrogen ◽  
Oxygen Species ◽  
Nitrogen Species ◽  
Extracellular Signal

Shear-induced reactive nitrogen species inhibit mitochondrial respiratory complex activities in cultured vascular endothelial cells

2007 ◽  
Vol 292 (3) ◽  
pp. C1103-C1112 ◽  
Author(s):  
Zhaosheng Han ◽  
Yeong-Renn Chen ◽  
Charles I. Jones ◽  
Guruguhan Meenakshisundaram ◽  
Jay L. Zweier ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Reactive Nitrogen Species ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Nitrogen Species ◽  
Laminar Shear Stress ◽  
Steady Laminar Shear Stress ◽  
Laminar Shear ◽  
Steady Laminar

There is evidence that nitric oxide (NO), superoxide (O2•−), and their associated reactive nitrogen species (RNS) produced by vascular endothelial cells (ECs) in response to hemodynamic forces play a role in cell signaling. NO is known to impair mitochondrial respiration. We sought to determine whether exposure of human umbilical vein ECs (HUVECs) to steady laminar shear stress and the resultant NO production modulate electron transport chain (ETC) enzymatic activities. The activities of respiratory complexes I, II/III, and IV were dependent on the presence of serum and growth factor supplement in the medium. EC exposure to steady laminar shear stress (10 dyn/cm2) resulted in a gradual inhibition of each of the complexes starting as early as 5 min from the flow onset and lasting up to 16 h. Ramp flow resulted in inhibition of the complexes similar to that of step flow. When ECs were sheared in the presence of the NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME; 100 μM), the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO; 100 μM), or the peroxynitrite (ONOO−) scavenger uric acid (UA; 50 μM), the flow-inhibitory effect on mitochondrial complexes was attenuated. In particular, l-NAME and UA abolished the flow effect on complex IV. Increased tyrosine nitration was observed in the mitochondria of sheared ECs, and UA blocked the shear-induced nitrotyrosine staining. In summary, shear stress induces mitochondrial RNS formation that inhibits the electron flux of the ETC at multiple sites. This may be a critical mechanism by which shear stress modulates EC signaling and function.

scholarly journals Reactive Nitrogen Species Is Required for the Activation of the AMP-activated Protein Kinase by Statin in Vivo

2008 ◽  
Vol 283 (29) ◽  
pp. 20186-20197 ◽  
Author(s):  
Hyoung Chul Choi ◽  
Ping Song ◽  
Zhonglin Xie ◽  
Yong Wu ◽  
Jian Xu ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Reactive Nitrogen Species ◽  
Reactive Nitrogen ◽  
Nitrogen Species ◽  
Amp Activated Protein Kinase

scholarly journals Withdrawal: Reactive nitrogen species is required for the activation of the AMP-activated protein kinase by statin in vivo.

2019 ◽  
Vol 294 (27) ◽  
pp. 10742-10742
Author(s):  
Hyoung Chul Choi ◽  
Ping Son ◽  
Zhonglin Xie ◽  
Yong Wu ◽  
Jian Xu ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Reactive Nitrogen Species ◽  
Reactive Nitrogen ◽  
Nitrogen Species ◽  
Amp Activated Protein Kinase

Glycated high-density lipoprotein regulates reactive oxygen species and reactive nitrogen species in endothelial cells

Metabolism ◽  
2003 ◽  
Vol 52 (1) ◽  
pp. 42-49 ◽  
Author(s):  
Toshiyuki Matsunaga ◽  
Takanori Nakajima ◽  
Takashi Miyazaki ◽  
Iwao Koyama ◽  
Shigeru Hokari ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
High Density Lipoprotein ◽  
Reactive Nitrogen Species ◽  
Density Lipoprotein ◽  
Reactive Oxygen ◽  
High Density ◽  
Reactive Nitrogen ◽  
Oxygen Species ◽  
Nitrogen Species

scholarly journals Eosinophil adhesion under flow conditions activates mechanosensitive signaling pathways in human endothelial cells

2005 ◽  
Vol 202 (6) ◽  
pp. 865-876 ◽  
Author(s):  
Susan L. Cuvelier ◽  
Smitha Paul ◽  
Neda Shariat ◽  
Pina Colarusso ◽  
Kamala D. Patel
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Protein Kinase ◽  
Leukocyte Adhesion ◽  
Focal Adhesions ◽  
Mitogen Activated Protein Kinase ◽  
Flow Conditions ◽  
Endothelial Cell Surface ◽  
Mitogen Activated Protein

Leukocyte transmigration can be affected by shear stress; however, the mechanisms by which shear stress modulates transmigration are unknown. We found that adhesion of eosinophils or an eosinophilic cell line to intereukin 4–stimulated endothelial cells led to a shear-dependent increase in endothelial cell intracellular calcium and increased phosphorylation of extracellular signal-regulated kinase (ERK) 2, but not c-Jun NH2-terminal kinase or p38 mitogen-activated protein kinase. Latex beads coated with antibodies were used to characterize the role of specific endothelial cell surface molecules in initiating signaling under shear conditions. We found that ligation of either vascular cell adhesion molecule–1 or E-selectin, but not major histocompatibility complex class I, induced a shear-dependent increase in ERK2 phosphorylation in cytokine-stimulated endothelial cells. Disassembly of the actin cytoskeleton with latrunculin A prevented ERK2 phosphorylation after adhesion under flow conditions, supporting a role for the cytoskeleton in mechanosensing. Rapid phosphorylation of focal adhesion kinase and paxillin occurred under identical conditions, suggesting that focal adhesions were also involved in mechanotransduction. Finally, we found that Rho-associated protein kinase and calpain were both critical in the subsequent transendothelial migration of eosinophils under flow conditions. These data suggest that ligation of leukocyte adhesion molecules under flow conditions leads to mechanotransduction in endothelial cells, which can regulate subsequent leukocyte trafficking.

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