Cytochalasin
Encyclopedia
Cytochalasins are fungal
metabolites that have the ability to bind to actin
filaments and block polymerization
and the elongation of actin. As a result of the inhibition of actin polymerization, cytochalasins can change cell
ular morphology, inhibit cellular processes such as cell division
, and even cause cells to undergo apoptosis
. Cytochalasins have the ability to permeate cell membranes, prevent cellular translocation and cause cells to enucleate. Cytochalasins can also have an effect on other aspects of biological processes unrelated to actin polymerization. For example, cytochalasin A and cytochalasin B can also inhibit the transport of monosaccharides across the cell membrane, cytochalasin H has been found to regulate plant growth, cytochalasin D
inhibits protein synthesis and cytochalasin E
prevents angiogenesis.
(CD) have found that the formation of CD-actin dimers, contain ATP-bound actin. These CD-actin dimers are reduced to CD-actin monomers as a result of ATP hydrolysis. The resulting CD-actin monomer can bind ATP-actin monomer to reform the CD-actin dimer. CD is very effective; only low concentrations (0.2 μM) are needed to prevent membrane ruffling and disrupt treadmilling
. The effects of many different cytochalasins had on actin filaments were analyzed and higher concentrations (2-20 μM) of CD were found to be needed to remove stress fibers.
Cytochalasin has found practical application in thromboelastometry
(TEM) whole blood assays for the assessment of fibrinogen
and fibrin polymerization disorders in the FIBTEM assay on ROTEM. This test is based on the principle that cytochalasin D
very effectively inhibits platelet
function by inhibition of the contractile elements. The platelet inhibition is more effective than when platelets are blocked by GPIIb/IIIa antagonists
. In vitro and clinical data indicate that the clot strength in FIBTEM increases in a fibrinogen
concentration-dependent manner independent of platelet count. Therefore fibrinogen deficiency or fibrin polymerization disorders can be rapidly detected.
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...
metabolites that have the ability to bind to actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
filaments and block polymerization
Polymerization
In polymer chemistry, polymerization is a process of reacting monomer molecules together in a chemical reaction to form three-dimensional networks or polymer chains...
and the elongation of actin. As a result of the inhibition of actin polymerization, cytochalasins can change cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
ular morphology, inhibit cellular processes such as cell division
Cell division
Cell division is the process by which a parent cell divides into two or more daughter cells . Cell division is usually a small segment of a larger cell cycle. This type of cell division in eukaryotes is known as mitosis, and leaves the daughter cell capable of dividing again. The corresponding sort...
, and even cause cells to undergo apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
. Cytochalasins have the ability to permeate cell membranes, prevent cellular translocation and cause cells to enucleate. Cytochalasins can also have an effect on other aspects of biological processes unrelated to actin polymerization. For example, cytochalasin A and cytochalasin B can also inhibit the transport of monosaccharides across the cell membrane, cytochalasin H has been found to regulate plant growth, cytochalasin D
Cytochalasin D
Cytochalasin D is a member of the class of mycotoxins known as cytochalasins. Cytochalasin D is an alkaloid produced by Helminthosporium and other molds....
inhibits protein synthesis and cytochalasin E
Cytochalasin E
Cytochalasin E, a member of the cytochalasin group, is an inhibitor of actin polymerization in blood platelets. It inhibits angiogenesis and tumor growth...
prevents angiogenesis.
Binding to actin filaments
Cytochalasins are known to bind to the barbed, fast growing plus ends of microfilaments, which then blocks both the assembly and disassembly of individual actin monomers from the bound end. Once bound, cytochalasins essentially cap the end of the new actin filament. One cytochalasin will bind to one actin filament. Studies done with cytochalasin DCytochalasin D
Cytochalasin D is a member of the class of mycotoxins known as cytochalasins. Cytochalasin D is an alkaloid produced by Helminthosporium and other molds....
(CD) have found that the formation of CD-actin dimers, contain ATP-bound actin. These CD-actin dimers are reduced to CD-actin monomers as a result of ATP hydrolysis. The resulting CD-actin monomer can bind ATP-actin monomer to reform the CD-actin dimer. CD is very effective; only low concentrations (0.2 μM) are needed to prevent membrane ruffling and disrupt treadmilling
Treadmilling
Treadmilling is a phenomenon observed in many cellular cytoskeletal filaments, especially in actin filaments and microtubules. It occurs when one end of a filament grows in length while the other end shrinks resulting in a section of filament seemingly "moving" across a stratum or the cytosol...
. The effects of many different cytochalasins had on actin filaments were analyzed and higher concentrations (2-20 μM) of CD were found to be needed to remove stress fibers.
Uses and applications of cytochalasins
Actin microfilaments have been widely studied using cytochalasins. Due to their chemical nature, cytochalasins can help researchers understand the importance of actin in various biological processes. The use of cytochalasins has allowed researchers to better understand actin polymerization, cell motility, ruffling, cell division, contraction, and cell stiffness. The use of cytochalasins has been so important to understanding cytoskeletal movement and many other biological processes, researchers have created two synthetic cytochalasins.Cytochalasin has found practical application in thromboelastometry
Thromboelastometry
Thromboelastometry is an established viscoelastic method for haemostatis testing in whole blood. TEM investigates the interaction of coagulation factors, their inhibitors, anticoagulant drugs, blood cells, specifically platelets, during clotting and subsequent fibrinolysis...
(TEM) whole blood assays for the assessment of fibrinogen
Fibrinogen
Fibrinogen is a soluble plasma glycoprotein, synthesised by the liver, that is converted by thrombin into fibrin during blood coagulation. This is achieved through processes in the coagulation cascade that activate the zymogen prothrombin to the serine protease thrombin, which is responsible for...
and fibrin polymerization disorders in the FIBTEM assay on ROTEM. This test is based on the principle that cytochalasin D
Cytochalasin D
Cytochalasin D is a member of the class of mycotoxins known as cytochalasins. Cytochalasin D is an alkaloid produced by Helminthosporium and other molds....
very effectively inhibits platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
function by inhibition of the contractile elements. The platelet inhibition is more effective than when platelets are blocked by GPIIb/IIIa antagonists
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
. In vitro and clinical data indicate that the clot strength in FIBTEM increases in a fibrinogen
Fibrinogen
Fibrinogen is a soluble plasma glycoprotein, synthesised by the liver, that is converted by thrombin into fibrin during blood coagulation. This is achieved through processes in the coagulation cascade that activate the zymogen prothrombin to the serine protease thrombin, which is responsible for...
concentration-dependent manner independent of platelet count. Therefore fibrinogen deficiency or fibrin polymerization disorders can be rapidly detected.