geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Erythropoietin employs cell longevity pathways of SIRT1 to foster endothelial vascular integrity during oxidant stress


, : Erythropoietin employs cell longevity pathways of SIRT1 to foster endothelial vascular integrity during oxidant stress. Current Neurovascular Research 8(3): 220-235

Given the cytoprotective ability of erythropoietin (EPO) in cerebral microvascular endothelial cells (ECs) and the invaluable role of ECs in the central nervous system, it is imperative to elucidate the cellular pathways for EPO to protect ECs against brain injury. Here we illustrate that EPO relies upon the modulation of SIRT1 (silent mating type information regulator 2 homolog 1) in cerebral microvascular ECs to foster cytoprotection during oxygen-glucose deprivation (OGD). SIRT1 activation which results in the inhibition of apoptotic early membrane phosphatidylserine (PS) externalization and subsequent DNA degradation during OGD becomes a necessary component for EPO protection in ECs, since inhibition of SIRT1 activity or diminishing its expression by gene silencing abrogates cell survival supported by EPO during OGD. Furthermore, EPO promotes the subcellular trafficking of SIRT1 to the nucleus which is necessary for EPO to foster vascular protection. EPO through SIRT1 averts apoptosis through activation of protein kinase B (Akt1) and the phosphorylation and cytoplasmic retention of the forkhead transcription factor FoxO3a. SIRT1 through EPO activation also utilizes mitochondrial pathways to prevent mitochondrial depolarization, cytochrome c release, and Bad, caspase 1, and caspase 3 activation. Our work identifies novel pathways for EPO in the vascular system that can govern the activity of SIRT1 to prevent apoptotic injury through Akt1, FoxO3a phosphorylation and trafficking, mitochondrial membrane permeability, Bad activation, and caspase 1 and 3 activities in ECs during oxidant stress.

US$29.90

PMID: 21722091


Other references

Jacob, J.-Paul.; Fouarge, J.-Paul., 1993: Evolution de l'effectif nicheur et habitats du petit gravelot (Charadrius dubius) en Wallonie et dans la region bruxelloise. Aves (Liege). 1992( ) juillet; 293-4: 113-136

Anonymous, 1994: Laboratory survey process changes for 1995. Joint Commission Perspectives. Joint Commission on Accreditation of Healthcare Organizations 14(5): 8-9, 12

Marchylo B.A.; Macgregor A.W., 1983: Separation of barley malt alpha amylase by chromato focusing. Chromatofocusing was used to resolve green malted barley .alpha.-amylase into individual components. Five peaks were eluted at 4.degree. C, whereas 4 peaks were eluted at room temperature (22.degree. C). Analysis of eluent fractions by polyacrylam...

Hao, P.; Jiang, F.; Cheng, J.; Ma, L.; Zhang, Y.; Zhao, Y., 2017: Traditional Chinese Medicine for Cardiovascular Disease: Evidence and Potential Mechanisms. Traditional Chinese medicine (TCM) has more than 2,000 years of history and has gained widespread clinical applications. However, the explicit role of TCM in preventing and treating cardiovascular disease remains unclear due to a lack of sound sci...

Senko, V., 1982: Process of specialization in crop and animal production Cooperatives, Czechoslovakia.1. Veterinarstvi 2(10): 433-435

Batra S., 1987: Increase by estrogen of calcium entry and calcium channel density in uterine smooth muscle. The effects of in vivo oestrogen treatment on both 45Ca influx in myometrial strips and the kinetics of [3H]-nitrendipine binding in the isolated plasma membrane (PM) was studied. After four days of continuous oestrogen treatment of ovariectomized...

Swanson, J.M.J.; Adcock, S.A.; McCammon, J.Andrew., 2005: Optimized Radii for Poisson-Boltzmann Calculations with the AMBER Force Field. Implicit solvent models are a standard tool for assessing the electrostatics of biomolecular systems. The accuracy of quantitative predictions, such as pKa values, transfer free energies, binding energies, and solvation forces, is strongly depende...

Goodbody, I., 1963: The biology of Aacidia nigra (Savigny). II. The development and survival of young ascidians. Biol, Woods Hole: 31-44

Malinoff, H.L.; Barkin, R.L.; Wilson, G., 2005: Sublingual buprenorphine is effective in the treatment of chronic pain syndrome. Many patients with chronic pain have less than optimal therapeutic outcomes after prolonged treatment with opiate analgesics. Worsening of pain perception, functional capacity, and mood often result. Medical detoxification is often undertaken in t...

Schutz R.; Delcaux C.; Balloul Delclaux E.; Pignol J., 1992: Treatment of empyema and pyopneumothorax of infectious origin and chronic evolution with drainage and lavage using iodised polyvinylpyrrolidine. Thirty five patients, twenty nine men and six women with a mean age of twenty six an suffering from a pyothorax 23% or a pyopneumothorax 77% of whom 41% had a bronchopleural fistula on chronic evolution (greater than one month before drainage), ha...