Trombospondina 1: Diferenzas entre revisións
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Liña 117:
Tanto o dominio de procoláxeno coma as repeticións de tipo I da TSP1 inhiben a neovascularización e a migración de [[célula endotelial|células endoteliais]]. Porén, é improbable que o mecanismo de acción destes dous fragmentos sexa o mesmo. As repeticións de tipo I da TSP1 poden inhibir a migración de células endoteliais nun ensaio en cámara de Boyden despois dunha exposición de 3-4 horas, mentres que cómpre un período de exposición de 36 a 48 horas para a inhibición da migración de células endoteliais co dominio de procoláxeno.<ref name="pmid7686555"/> Mentres que os ensaios da membrana corioalantoica (CAM) indican que as repeticións de tipo I da TSP1 son anxioxénicas, tamén indican que a secuencia de procoláxeno carece de actividade antianxioxénica. Isto pode deberse en parte a que o extremo animo terminal da TSP1 difire máis que o carboxilo terminal entre especies, pero pode tamén suxerir diferentes mecanismos de acción.<ref name="pmid10500044">{{cite journal | vauthors = Iruela-Arispe ML, Lombardo M, Krutzsch HC, Lawler J, Roberts DD | title = Inhibition of angiogenesis by thrombospondin-1 is mediated by 2 independent regions within the type 1 repeats | journal = Circulation | volume = 100 | issue = 13 | pages = 1423–31 | date = Sep 1999 | pmid = 10500044 | doi = 10.1161/01.cir.100.13.1423 | url = http://circ.ahajournals.org/cgi/content/abstract/100/13/1423 }}</ref>
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TSP1 contains three type I repeats, only the second two of which have been found to inhibit [[angiogenesis]]. The type I repeat motif is more effective than the entire protein at inhibiting angiogenesis and contains not one but two regions of activity. The amino-terminal end contains a tryptophan-rich motif that blocks [[fibroblast growth factor]] (FGF-2 or bFGF) driven angiogenesis. This region has also been found to prevent FGF-2 binding [[endothelial cells|ECs]], suggesting that its mechanism of action may be to sequester FGF-2. The second region of activity, the CD36 binding region of TSP1, can be found on the carboxy-terminal half of the type I repeats.<ref name="pmid10500044"/> It has been suggested that activating the CD36 receptor causes an increase in ECs sensitivity to apoptotic signals.<ref name="pmid9135017">{{cite journal | vauthors = Guo N, Krutzsch HC, Inman JK, Roberts DD | title = Thrombospondin 1 and type I repeat peptides of thrombospondin 1 specifically induce apoptosis of endothelial cells | journal = Cancer Research | volume = 57 | issue = 9 | pages = 1735–42 | date = May 1997 | pmid = 9135017 | doi = | url = http://cancerres.aacrjournals.org/cgi/content/abstract/57/9/1735 }}</ref><ref name="pmid15036264">{{cite journal | vauthors = Sid B, Sartelet H, Bellon G, El Btaouri H, Rath G, Delorme N, Haye B, Martiny L | title = Thrombospondin 1: a multifunctional protein implicated in the regulation of tumor growth | journal = Critical Reviews in Oncology/Hematology | volume = 49 | issue = 3 | pages = 245–58 | date = Mar 2004 | pmid = 15036264 | doi = 10.1016/j.critrevonc.2003.09.009 }}</ref> Type I repeats have also been shown to bind to [[heparin]], [[fibronectin]], [[TGF beta|TGF-β]], and others, potentially antagonizing the effects of these molecules on ECs.<ref name="pmid9679984">{{cite journal | vauthors = Guo N, Zabrenetzky VS, Chandrasekaran L, Sipes JM, Lawler J, Krutzsch HC, Roberts DD | title = Differential roles of protein kinase C and pertussis toxin-sensitive G-binding proteins in modulation of melanoma cell proliferation and motility by thrombospondin 1 | journal = Cancer Research | volume = 58 | issue = 14 | pages = 3154–62 | date = Jul 1998 | pmid = 9679984 | doi = | url = http://cancerres.aacrjournals.org/cgi/content/abstract/58/14/3154 }}</ref> However, CD36 is generally considered to be the dominant inhibitory signaling receptor for TSP1, and [[endothelial cells|EC]] expression of CD36 is restricted to microvascular ECs.▼
▲A TSP1
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Soluble type I repeats have been shown to decrease EC numbers by inhibiting proliferation and promoting apoptosis. Attachment of [[endothelial cells]] to [[fibronectin]] partially reverses this phenomenon. However this domain is not without a two-faced nature of its own. Bound protein fragments of the type I repeats have been shown to serve as attachment factors for both [[endothelial cells|ECs]] and melanoma cells.<ref name="pmid1999454">{{cite journal | vauthors = Prater CA, Plotkin J, Jaye D, Frazier WA | title = The properdin-like type I repeats of human thrombospondin contain a cell attachment site | journal = The Journal of Cell Biology | volume = 112 | issue = 5 | pages = 1031–40 | date = Mar 1991 | pmid = 1999454 | pmc = 2288870 | doi = 10.1083/jcb.112.5.1031 }}</ref>
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