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Structural and functional aspects of liver sinusoidal endothelial cell fenestrae: a review.

Braet F, Wisse E - Comp Hepatol (2002)

Bottom Line: This review provides a detailed overview of the current state of knowledge about the ultrastructure and dynamics of liver sinusoidal endothelial fenestrae.Various aspects of liver sinusoidal endothelial fenestrae regarding their structure, origin, species specificity, dynamics and formation will be explored.In addition, the role of liver sinusoidal endothelial fenestrae in relation to lipoprotein metabolism, fibrosis and cancer will be approached.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory for Cell Biology and Histology, Free University of Brussels (VUB), Laarbeeklaan 103, 1090 Brussels-Jette, Belgium. filipbra@cyto.vub.ac.be

ABSTRACT
This review provides a detailed overview of the current state of knowledge about the ultrastructure and dynamics of liver sinusoidal endothelial fenestrae. Various aspects of liver sinusoidal endothelial fenestrae regarding their structure, origin, species specificity, dynamics and formation will be explored. In addition, the role of liver sinusoidal endothelial fenestrae in relation to lipoprotein metabolism, fibrosis and cancer will be approached.

No MeSH data available.


Related in: MedlinePlus

Scheme of the serotonin signal pathway showing the steps in fenestral contraction and relaxation, as postulated by Gatmaitan et al.[89,90,104]: Serotonin binds to a ketanserin-inhibitable receptor, coupled to a pertussis-toxin sensitive G-protein; a calcium channel opens, causing an influx of calcium ions; the intracellular calcium level increases rapidly, and calcium binds to calmodulin; the calcium-calmodulin complex activates myosin light chain kinase, and as a result phosphorylation of the 20-kd light chain of myosin occurs, resulting in an increased actin-activated myosin ATPase activity, which finally initiates contraction of fenestrae. The mechanism for the relaxation of LSEC fenestrae is presently unclear and probably involves dephosphorylation of myosin light chains as represented by dashed lines: a decrease in the cytosolic free calcium concentration leads to dissociation of calcium and calmodulin from the kinase, thereby inactivating myosin light chain kinase, under these conditions myosin light chain phosphatase, which is not dependent on calcium for activity, dephosphorylates myosin light chain and finally causes relaxation of fenestrae.
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Figure 3: Scheme of the serotonin signal pathway showing the steps in fenestral contraction and relaxation, as postulated by Gatmaitan et al.[89,90,104]: Serotonin binds to a ketanserin-inhibitable receptor, coupled to a pertussis-toxin sensitive G-protein; a calcium channel opens, causing an influx of calcium ions; the intracellular calcium level increases rapidly, and calcium binds to calmodulin; the calcium-calmodulin complex activates myosin light chain kinase, and as a result phosphorylation of the 20-kd light chain of myosin occurs, resulting in an increased actin-activated myosin ATPase activity, which finally initiates contraction of fenestrae. The mechanism for the relaxation of LSEC fenestrae is presently unclear and probably involves dephosphorylation of myosin light chains as represented by dashed lines: a decrease in the cytosolic free calcium concentration leads to dissociation of calcium and calmodulin from the kinase, thereby inactivating myosin light chain kinase, under these conditions myosin light chain phosphatase, which is not dependent on calcium for activity, dephosphorylates myosin light chain and finally causes relaxation of fenestrae.

Mentions: Van Der Smissen et al. [51] and Oda et al. [102] postulated at first in 1986 that a calcium-calmodulin-actomyosin system around fenestrae has probably a key role in the regulation of the fenestral diameter. This hypothesis was nicely proven in subsequent years by studying the role of calcium ions and calmodulin in fenestrae regulation using immunoelectron microscopy [99,101], electron microprobe analysis [102], microfluometric digital image analysis [40] and patch clamp technique [88]. Oda et al. [103] showed that the addition of a calcium ionophore to LSEC induced fenestral contraction. This contraction could be suppressed by chelating extracellular calcium or by pretreatment of LSEC with a calmodulin antagonist, demonstrating the messenger function of calcium ions and the role of the intracellular Ca2+-receptor calmodulin in the fenestrae diameter regulation. In addition, Arias [83] and Arias et al. [83,100] demonstrated that the serotonin induced contraction of fenestrae occurs together with phosphorylation of the 20-kd subunit of myosin light chain kinase. All these findings suggest the crucial role of a calcium-calmodulin-actomyosin complex in the regulation of the fenestral diameter [40] (Fig. 3).


Structural and functional aspects of liver sinusoidal endothelial cell fenestrae: a review.

Braet F, Wisse E - Comp Hepatol (2002)

Scheme of the serotonin signal pathway showing the steps in fenestral contraction and relaxation, as postulated by Gatmaitan et al.[89,90,104]: Serotonin binds to a ketanserin-inhibitable receptor, coupled to a pertussis-toxin sensitive G-protein; a calcium channel opens, causing an influx of calcium ions; the intracellular calcium level increases rapidly, and calcium binds to calmodulin; the calcium-calmodulin complex activates myosin light chain kinase, and as a result phosphorylation of the 20-kd light chain of myosin occurs, resulting in an increased actin-activated myosin ATPase activity, which finally initiates contraction of fenestrae. The mechanism for the relaxation of LSEC fenestrae is presently unclear and probably involves dephosphorylation of myosin light chains as represented by dashed lines: a decrease in the cytosolic free calcium concentration leads to dissociation of calcium and calmodulin from the kinase, thereby inactivating myosin light chain kinase, under these conditions myosin light chain phosphatase, which is not dependent on calcium for activity, dephosphorylates myosin light chain and finally causes relaxation of fenestrae.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC131011&req=5

Figure 3: Scheme of the serotonin signal pathway showing the steps in fenestral contraction and relaxation, as postulated by Gatmaitan et al.[89,90,104]: Serotonin binds to a ketanserin-inhibitable receptor, coupled to a pertussis-toxin sensitive G-protein; a calcium channel opens, causing an influx of calcium ions; the intracellular calcium level increases rapidly, and calcium binds to calmodulin; the calcium-calmodulin complex activates myosin light chain kinase, and as a result phosphorylation of the 20-kd light chain of myosin occurs, resulting in an increased actin-activated myosin ATPase activity, which finally initiates contraction of fenestrae. The mechanism for the relaxation of LSEC fenestrae is presently unclear and probably involves dephosphorylation of myosin light chains as represented by dashed lines: a decrease in the cytosolic free calcium concentration leads to dissociation of calcium and calmodulin from the kinase, thereby inactivating myosin light chain kinase, under these conditions myosin light chain phosphatase, which is not dependent on calcium for activity, dephosphorylates myosin light chain and finally causes relaxation of fenestrae.
Mentions: Van Der Smissen et al. [51] and Oda et al. [102] postulated at first in 1986 that a calcium-calmodulin-actomyosin system around fenestrae has probably a key role in the regulation of the fenestral diameter. This hypothesis was nicely proven in subsequent years by studying the role of calcium ions and calmodulin in fenestrae regulation using immunoelectron microscopy [99,101], electron microprobe analysis [102], microfluometric digital image analysis [40] and patch clamp technique [88]. Oda et al. [103] showed that the addition of a calcium ionophore to LSEC induced fenestral contraction. This contraction could be suppressed by chelating extracellular calcium or by pretreatment of LSEC with a calmodulin antagonist, demonstrating the messenger function of calcium ions and the role of the intracellular Ca2+-receptor calmodulin in the fenestrae diameter regulation. In addition, Arias [83] and Arias et al. [83,100] demonstrated that the serotonin induced contraction of fenestrae occurs together with phosphorylation of the 20-kd subunit of myosin light chain kinase. All these findings suggest the crucial role of a calcium-calmodulin-actomyosin complex in the regulation of the fenestral diameter [40] (Fig. 3).

Bottom Line: This review provides a detailed overview of the current state of knowledge about the ultrastructure and dynamics of liver sinusoidal endothelial fenestrae.Various aspects of liver sinusoidal endothelial fenestrae regarding their structure, origin, species specificity, dynamics and formation will be explored.In addition, the role of liver sinusoidal endothelial fenestrae in relation to lipoprotein metabolism, fibrosis and cancer will be approached.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory for Cell Biology and Histology, Free University of Brussels (VUB), Laarbeeklaan 103, 1090 Brussels-Jette, Belgium. filipbra@cyto.vub.ac.be

ABSTRACT
This review provides a detailed overview of the current state of knowledge about the ultrastructure and dynamics of liver sinusoidal endothelial fenestrae. Various aspects of liver sinusoidal endothelial fenestrae regarding their structure, origin, species specificity, dynamics and formation will be explored. In addition, the role of liver sinusoidal endothelial fenestrae in relation to lipoprotein metabolism, fibrosis and cancer will be approached.

No MeSH data available.


Related in: MedlinePlus