Regulation of angiotensin II-stimulated osteopontin expression in cardiac microvascular endothelial cells: Role of p42/44 mitogen-activated protein kinase and reactive oxygen species

2001 ◽  
Vol 188 (1) ◽  
pp. 132-138 ◽  
Author(s):  
Zhonglin Xie ◽  
David R. Pimental ◽  
Seema Lohan ◽  
Alla Vasertriger ◽  
Christina Pligavko ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Angiotensin Ii ◽  
Mitogen Activated Protein Kinase ◽  
Microvascular Endothelial Cells ◽  
Oxygen Species ◽  
Osteopontin Expression ◽  
Mitogen Activated Protein ◽  
Cardiac Microvascular Endothelial Cells

scholarly journals Essential Role of STAT1 in Caspase-Independent Cell Death of Activated Macrophages through the p38 Mitogen-Activated Protein Kinase/STAT1/Reactive Oxygen Species Pathway

2005 ◽  
Vol 25 (15) ◽  
pp. 6821-6833 ◽  
Author(s):  
Hun Sik Kim ◽  
Myung-Shik Lee
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
P38 Mapk ◽  
Serine Phosphorylation ◽  
Mitogen Activated Protein Kinase ◽  
Oxygen Species ◽  
Activated Macrophages ◽  
Caspase Activation ◽  
Mitogen Activated Protein

ABSTRACT Unlike other immune cells, activation of macrophages by stimulating agents, such as lipopolysaccharide (LPS), confers significant resistance to many apoptotic stimuli, but the underlying mechanism of this phenomenon remains largely unknown. Here, we demonstrate that LPS-induced early caspase activation is essential for macrophage survival because blocking caspase activation with a pancaspase inhibitor (zVAD [benzyloxycarbonyl-Val-Ala-Asp]) rapidly induced death of activated macrophages. This type of death process by zVAD/LPS was principally mediated by intracellular generation of superoxide. STAT1 knockout macrophages demonstrated profoundly decreased superoxide production and were resistant to treatment with zVAD/LPS, indicating the crucial involvement of STAT1 in macrophage death by zVAD/LPS. STAT1 level and activity were reciprocally regulated by caspase activation and were associated with cell death. Activation of STAT1 was critically dependent upon serine phosphorylation induced by p38 mitogen-activated protein kinase (MAPK) because a p38 MAPK inhibitor nullified STAT1 serine phosphorylation, reactive oxygen species (ROS) production, and macrophage death by zVAD/LPS. Conversely, p38 MAPK activation was dependent upon superoxide and was also nullified in STAT1 knockout macrophages, probably due to impaired generation of superoxide. Our findings collectively indicate that STAT1 signaling modulates intracellular oxidative stress in activated macrophages through a positive-feedback mechanism involving the p38 MAPK/STAT1/ROS pathway, which is interrupted by caspase activation. Furthermore, our study may provide significant insights in regards to the unanticipated critical role of STAT1 in the caspase-independent death pathway.

scholarly journals NPC-EXs Alleviate Endothelial Oxidative Stress and Dysfunction through the miR-210 Downstream Nox2 and VEGFR2 Pathways

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Hua Liu ◽  
Jinju Wang ◽  
Yusen Chen ◽  
Yanfang Chen ◽  
Xiaotang Ma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Angiotensin Ii ◽  
Neural Progenitor Cells ◽  
Tube Formation ◽  
Oxygen Species ◽  
Protective Effects ◽  
Ang Ii

We have demonstrated that neural progenitor cells (NPCs) protect endothelial cells (ECs) from oxidative stress. Since exosomes (EXs) can convey the benefit of parent cells through their carried microRNAs (miRs) and miR-210 is ubiquitously expressed with versatile functions, we investigated the role of miR-210 in the effects of NPC-EXs on oxidative stress and dysfunction in ECs. NPCs were transfected with control and miR-210 scramble/inhibitor/mimic to generate NPC-EXscon, NPC-EXssc, NPC-EXsanti-miR-210, and NPC-EXsmiR-210. The effects of various NPC-EXs on angiotensin II- (Ang II-) induced reactive oxygen species (ROS) overproduction, apoptosis, and dysfunction, as well as dysregulation of Nox2, ephrin A3, VEGF, and p-VEGFR2/VEGFR2 in ECs were evaluated. Results showed (1) Ang II-induced ROS overproduction, increase in apoptosis, and decrease in tube formation ability, accompanied with Nox2 upregulation and reduction of p-VEGFR2/VEGFR2 in ECs. (2) Compared to NPC-EXscon or NPC-EXssc, NPC-EXsanti-miR-210 were less whereas NPC-EXsmiR-210 were more effective on attenuating these detrimental effects induced by Ang II in ECs. (3) These effects of NPC-EXsanti-miR-210 and NPC-EXsmiR-210 were associated with the changes of miR-210, ephrin A3, VEGF, and p-VEGFR2/VEGFR2 ratio in ECs. Altogether, the protective effects of NPC-EXs on Ang II-induced endothelial injury through miR-210 which controls Nox2/ROS and VEGF/VEGFR2 signals were studied.

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