Inhibition of fibrinolysis by cellular glutathione depletion in the rabbit

Lasierra, J; Aza, M.J.; Collado, Pilar S.; González, Julia García; Esteller, A

doi:10.1016/0049-3848(89)90313-7

Cited by 3 publications

(10 citation statements)

References 25 publications

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“…BSO inhibits GSH biosynthesis and causes depletion of cellular GSH levels 21,22. In rats, the same GSH decrease has also been achieved with the administration of diethyl maleate – the diethyl maleate reacts with GSH, causing the formation of conjugated GSH, which is then excreted 31,62–64…”

Section: Brain Gshmentioning

confidence: 91%

“…A study of the fibrinolytic activity in the aortic arch revealed an extensive area of lysis in the endothelial wall in the control rabbit groups 62. Following an administration of BSO, fibrinolysis was inhibited (Figure 1A and B) and only reappeared 3 days later.…”

Section: Fibrinolytic Activity and Gshmentioning

confidence: 93%

“…Buthionine sulfoximine (S-(n-butyl) homocysteine sulfoximine) (BSO), a selective and potent inhibitor of the gamma-glutamylcysteine synthetase,24,62 has been administered in previous investigations. BSO inhibits GSH biosynthesis and causes depletion of cellular GSH levels 21,22.…”

Section: Brain Gshmentioning

confidence: 99%

“…More than 20 years ago62 it was reported that the pharmacological effect of administration of BSO or diethyl maleate in rabbits is a significant decrease in GSH levels, accompanied by the inhibition of fibrinolytic activity important for the fibrin plate. This inhibition of plasmin activity results from a decrease in the liberation of t-PA at the cellular level and a significant increase in its inhibitor, plasminogen activator inhibitor (PAI-1), and occurs without any modification in the normal values of alpha-2 antiplasmin.…”

Section: Fibrinolytic Activity and Gshmentioning

confidence: 99%

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Beta-amyloidolysis and glutathione in Alzheimer's disease

J¹,

Coronel²,

Aza³

et al. 2013

JBM

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In this review, we hypothesized the importance of the interaction between the brain glutathione (GSH) system, the proteolytic tissue plasminogen activator (t-PA)/plasminogen/ plasmin system, regulated by plasminogen activator inhibitor (PAI-1), and neuroserpin in the pathogenesis of Alzheimer’s disease. The histopathological characteristic hallmark that gives personality to the diagnosis of Alzheimer’s disease is the accumulation of neurofibroid tangles located intracellularly in the brain, such as the protein tau and extracellular senile plaques made primarily of amyloidal substance. These formations of complex etiology are intimately related to GSH, brain protective antioxidants, and the proteolytic system, in which t-PA plays a key role. There is scientific evidence that suggests a relationship between aging, a number of neurodegenerative disorders, and the excessive production of reactive oxygen species and accompanying decreased brain proteolysis. The plasminogen system in the brain is an essential proteolytic mechanism that effectively degrades amyloid peptides (“beta-amyloidolysis”) through action of the plasmin, and this physiologic process may be considered to be a means of prevention of neurodegenerative disorders. In parallel to the decrease in GSH levels seen in aging, there is also a decrease in plasmin brain activity and a progressive decrease of t-PA activity, caused by a decrease in the expression of the t-PA together with an increase of the PAI-1 levels, which rise to an increment in the production of amyloid peptides and a lesser clearance of them. Better knowledge of the GSH mechanism and cerebral proteolysis will allow us to hypothesize about therapeutic practices.

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Section: Brain Gshmentioning

confidence: 91%

Section: Fibrinolytic Activity and Gshmentioning

confidence: 93%

Section: Brain Gshmentioning

confidence: 99%

Section: Fibrinolytic Activity and Gshmentioning

confidence: 99%

See 2 more Smart Citations

Beta-amyloidolysis and glutathione in Alzheimer's disease

J¹,

Coronel²,

Aza³

et al. 2013

JBM

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show abstract

“…We reported, in fact, that the pharmacological effect that is obtained after the administration of buthionine sulfoximine (BSO) or dietil maleate in rabbits, is a significant decrease in the levels of GSH with the inhibition of fibrinolytic activity measured in the fibrin plates, due to a decrease of cellular t-PA release with a significant increase of its inhibitor PAI-1 [13] [127].…”

Section: Discussionmentioning

confidence: 99%

Sulodexide and Alzheimer’s Disease: A Preliminary Prospective Study

J¹,

Pascual-Salcedo²,

Aza-Pascual-Salcedo³

2016

WJCD

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The purpose of this prospective study is to determine the relative incidence of Alzheimer's disease in patients treated for at least three years, with sulodexide (n = 46, 76.48 ± 7.02 years old) or acenocoumarol (n = 47, 78.21 ± 6.66 years old) in order to prevent primary and secondary venous thromboembolism and atherothrombotic disease. In the sulodexide group, there was an apparent prevention of cognitive and behavioural impairment (relative incidence: 2.02) compared with acenocoumarol group (relative incidence: 4.86). The favourable results in sulodexide group may be related to their pharmacodynamic actions of inhibition of PAI-1, which may interfere with the pathogenesis of Alzheimer's disease, and to the role of glutathione and PAI-1 in the β-amyloid system in the brain.

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Aging: Thromboembolic Disease, Metabolic Syndrome, Type 2 Diabetes Mellitus, and Alzheimer’s Disease

J¹,

Pascual-Salcedo²,

Lasierra-Ibañez³

et al. 2016

JBM

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Aging can be interpreted as an unavoidable process whose end point is the death. Aging entails, in the hemostasis field, some changes that favour blood hypercoagulability. Both the plasminogen activator inhibitor (PAI-1), specific inhibitor of the tissue plasminogen activator (t-PA), accompanied by the oxidative stress and the marked decrease of the main antioxidant-glutathione are fundamental in the bases of elderly pathologies which can cause death. There is some scientific evidence of the relationship between aging, neuro-degenerative diseases, an excessive production of reactive oxygen species and the decrease of proteolysis in brain. The cerebral plasminogen/plasmin system represents the essential proteolytic mechanism that degrades amyloid peptides (βamyloidosis) for action of plasmin with effectiveness. This physiologic process is being considered as a preventive neurodegenerative mechanism. At the same time, the decrease of glutathione levels in aging entails a decrease of cerebral plasmin activity and a progressive descent of t-PA activity due to a descent in t-PA expression and an increase in PAI production. All of them entail an increment of amyloid beta peptides (Aβ) production and a lower level of their clearance. Both mechanisms, oxidative stress, direct consequence of the oxygenate metabolism of aerobics cells, and changes in the systemic fibrinolysis and cerebral b-amyloidolytic activity, play a very important role in thromboembolic disease, metabolic syndrome-obesity, insulin resistance, hyperglycemia-, type 2 Diabetes Mellitus and Alzheimer's disease, clinical processes that accompany the aging. In this revision we show the importance of the interaction between glutathione, proteolytic t-PA/plasminogen/plasmin system, and the inhibitor PAI-1 in aging physiopathology, whose results suggest the hypothesis of the importance of a therapeutic strategy using the inhibition of

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Inhibition of fibrinolysis by cellular glutathione depletion in the rabbit

Cited by 3 publications

References 25 publications

Beta-amyloidolysis and glutathione in Alzheimer's disease

Beta-amyloidolysis and glutathione in Alzheimer's disease

Sulodexide and Alzheimer’s Disease: A Preliminary Prospective Study

Aging: Thromboembolic Disease, Metabolic Syndrome, Type 2 Diabetes Mellitus, and Alzheimer’s Disease

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Inhibition of fibrinolysis by cellular glutathione depletion in the rabbit

Cited by 3 publications

References 25 publications

Beta-amyloidolysis and glutathione in Alzheimer&#39;s disease

Beta-amyloidolysis and glutathione in Alzheimer&#39;s disease

Sulodexide and Alzheimer’s Disease: A Preliminary Prospective Study

Aging: Thromboembolic Disease, Metabolic Syndrome, Type 2 Diabetes Mellitus, and Alzheimer’s Disease

Contact Info

Product

Resources

About

Beta-amyloidolysis and glutathione in Alzheimer's disease

Beta-amyloidolysis and glutathione in Alzheimer's disease