Effect of ascorbate on plasminogen activator inhibitor-1 expression and release from platelets and endothelial cells in an in-vitro model of sepsis

Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis
Scott B SwarbreckKarel Tyml

Abstract

The microcirculation during sepsis fails due to capillary plugging involving microthrombosis. We demonstrated that intravenous injection of ascorbate reduces this plugging, but the mechanism of this beneficial effect remains unclear. We hypothesize that ascorbate inhibits the release of the antifibrinolytic plasminogen activator inhibitor-1 (PAI-1) from endothelial cells and platelets during sepsis. Microvascular endothelial cells and platelets were isolated from mice. Cells were cultured and stimulated with lipopolysaccharide (LPS), tumor necrosis factor alpha (TNFα), or thrombin (agents of sepsis), with/without ascorbate for 1-24 h. PAI-1 mRNA was determined by quantitative PCR. PAI-1 protein release into the culture medium was measured by ELISA. In platelets, PAI-1 release was measured after LPS, TNFα, or thrombin stimulation, with/without ascorbate. In endothelial cells, LPS and TNFα increased PAI-1 mRNA after 6-24 h, but no increase in PAI-1 release was observed; ascorbate did not affect these responses. In platelets, thrombin, but not LPS or TNFα, increased PAI-1 release; ascorbate inhibited this increase at low extracellular pH. In unstimulated endothelial cells and platelets, PAI-1 is released into the extracellular spa...Continue Reading

References

Jul 1, 1984·Infection and Immunity·R S McCuskeyB Urbaschek
Feb 2, 1996·The Journal of Biological Chemistry·I M Lang, R R Schleef
Nov 11, 1998·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·A SagripantiG Barsotti
Aug 19, 1999·The New England Journal of Medicine·M Levi, H Ten Cate
Oct 30, 2001·Journal of Investigative Surgery : the Official Journal of the Academy of Surgical Research·H FreiseH U Spiegel
Nov 18, 2003·The Journal of Clinical Investigation·Beatrice CambienDenisa D Wagner
Feb 5, 2004·Journal of Thrombosis and Thrombolysis·Marcel LeviTom van der Poll
Nov 15, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Rolando E RumbautAlan R Burns
May 12, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Rebecca L McKinnonKarel Tyml
Jan 22, 2010·Cellular and Molecular Life Sciences : CMLS·Steven W Kerrigan, Dermot Cox
Feb 4, 2010·Critical Care Medicine·Stephen TrzeciakUNKNOWN Emergency Medicine Shock Research Network (EMShockNet) investigators
Nov 10, 2011·PloS One·Helén BrogrenSverker Jern
Apr 24, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Bernard J FisherRamesh Natarajan
Feb 14, 2013·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Dan SecorKarel Tyml
Aug 7, 2013·JPEN. Journal of Parenteral and Enteral Nutrition·Bernard J FisherRamesh Natarajan
Sep 12, 2013·Virulence·Mitchell P Fink

❮ Previous
Next ❯

Citations

Feb 23, 2017·World Journal of Critical Care Medicine·Bassem M MohammedRamesh Natarajan
Nov 18, 2020·Antioxidants & Redox Signaling·Lucie Aumailley, Michel Lebel
Aug 10, 2021·Journal of Cellular Physiology·Maria E C BrunoMarlene E Starr

❮ Previous
Next ❯

Methods Mentioned

BETA
ELISA
PCR

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.