The immunosuppressant drug FK506 prevents Fas-induced apoptosis in human hepatocytes

Gómez‐Lechón, M. José; Serralta, Alfonso; Donato, M. Teresa; Jiménez, Núria; O’Connor, Enrique; Castell, José V.; Mir, José

doi:10.1016/j.bcp.2004.08.028

Cited by 29 publications

(14 citation statements)

References 36 publications

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“…In this study, tacrolimus signifi cantly suppressed Fas-mediated apoptotic cell death and caspase-3 activation, in addition to IL-8 production from A549 cells. These results support previous studies indicating that tacrolimus prevents Fas-induced apoptosis and caspase-3 activation in human [39]. In a preliminary study, we have obtained evidence that rapamycin (10-1000 ng/ml) antagonized the inhibitory actions of FK506 against A23187-and Fas-mediated IL-8 production in A549 cells.…”

Section: Discussionsupporting

confidence: 78%

FK506 (tacrolimus) improves lung injury through inhibition of Fas-mediated inflammation

2006

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Section: Discussionsupporting

confidence: 78%

FK506 (tacrolimus) improves lung injury through inhibition of Fas-mediated inflammation

2006

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“…Studies conducted with various cell types have refined knowledge of the central role played by changes in intracellular Ca 2+ in mediating apoptotic cell death (48,62,(88)(89)(90)(91)(92)(93)(94)(95)(96)(97)(98)(99). Thus evidence has been obtained to indicate that in the early stages of the apoptotic pathway, an increase in [Ca 2+ ] cyt leads to the uptake of Ca 2+ by mitochondria, which, together with proteins which modulate apoptosis (including Bcl-2, Bcl-X, and Mcl-L; Bad, Bid, and Bim; and Bax and Bak), causes the release of cytochrome c from the intramembrane mitochondrial space via pores in the outer mitochondrial membrane ( Figure 4B).…”

Section: Intracellular Ca 2+ As a Mediator Of Hepatocyte Injury Inducmentioning

confidence: 99%

Hepatic Ischemia-Reperfusion Injury: Roles of Ca2+ and Other Intracellular Mediators of Impaired Bile Flow and Hepatocyte Damage

et al. 2006

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Liver resection and liver transplantation have been successful in the treatment of liver tumors and end-stage liver disease. This success has led to an expansion in the pool of patients potentially treatable by liver surgery and, in the case of transplantation, to a shortage of liver donors. At present, there are significant numbers of potential candidates for liver resection and liver donation who have fatty livers, are aged, or have livers damaged by chemotherapy. All of these are at high risk for ischemic reperfusion (IR) injury. The aims of this review are to assess current knowledge of the clinical effectiveness of ischemic preconditioning and intermittent ischemia in reducing IR damage in liver surgery; to evaluate the use of bile flow as a sensitive indicator of IR liver damage; and to analyze the molecular mechanisms, especially intracellular Ca2+, involved in IR injury and ischemic preconditioning. It is concluded that bile flow is a sensitive indicator of IR injury. Together with reactive oxygen species (ROS) and other extracellular and intracellular signaling molecules, intracellular Ca2+ in hepatocytes plays a key role in the normal regulation of bile flow and in IR-induced injury and cell death. Ischemic preconditioning is an effective strategy to reduce IR injury but there is considerable scope for improvement, especially in patients with fatty and aged livers. The development of effective new strategies to reduce IR injury will depend on improved understanding of the molecular mechanisms involved, especially by gaining a better perspective of the relative importance of the various intrahepatocyte signaling pathways involved.

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“…The application of FK506 (tacrolimus) in vivo is associated with a reduction of ROS (29). FK506 (tacrolimus) has also been found to exert anti-apoptotic effects by preventing Fas-induced apoptosis in human hepatocytes in vitro (33), as well as in an in vivo model of IRI in rats (34). A decrease in liver apoptosis may contribute to persisting protection of cellular integrity.…”

Section: Discussionmentioning

confidence: 99%

Experimental Studies on Protective Effects of FK506 Against Hepatic Ischemia-Reperfusion Injury

Sawada

Inoue

Tanabe³

et al. 2016

J. Med. Invest.

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: Purposes ; FK506 (strong immunosuppressive agent) was investigated experimentally whether to protect the hepatic IRI. Methods ; Warm ischemic experiment using pigs and rats were performed and examined whether FK506 is effective. Results ; The results obtained are as follows. 1. Warm ischemia allowed time of the pigs without FK506 was 150 minutes, but as for that of FK506 group, the extension of 30 minutes was got in 180 minutes. 2. Biliary excretion rate of BSP after reperfusion were better in the group of 180 minutes ischemia with FK506 than in without FK506 group. 3. Chemiluminescence intensity in the peripheral neutrophils and adhered and infiltrated leukocytes in the liver were suppressed markedly by FK506. 4. The vascular endothelium with the scanning electron microscope was relatively preserved in the FK506 group comparing to the placebo group on 30 minutes after reperfusion. 5. Stress gastric ulcer was controlled and myeloperoxidase activity in the gastric mucosa was suppressed by FK506. Conclusion ; Based on the results of theses experiments, it was suggested that FK506 has a protective effect on IRI by suppressing : the impairment of sinusoidal endothelial cells ; the activation of KCs ; the disturbance of micro-circulation ; oxidative stress ; inflammation ; and the accumulation of leukocytes.

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The immunosuppressant drug FK506 prevents Fas-induced apoptosis in human hepatocytes

Cited by 29 publications

References 36 publications

FK506 (tacrolimus) improves lung injury through inhibition of Fas-mediated inflammation

FK506 (tacrolimus) improves lung injury through inhibition of Fas-mediated inflammation

Hepatic Ischemia-Reperfusion Injury: Roles of Ca2+ and Other Intracellular Mediators of Impaired Bile Flow and Hepatocyte Damage

Experimental Studies on Protective Effects of FK506 Against Hepatic Ischemia-Reperfusion Injury

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