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Typus
BauernOpfer
Bearbeiter
Hindemith
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Untersuchte Arbeit:
Seite: 24, Zeilen: 6-19
Quelle: Bedard Krause 2007
Seite(n): 249, 250, Zeilen: 249: l.col: 16ff
The activation of Nox2 occurs through a complex series of protein/protein interactions, where Nox2 constitutively associates with p22phox, forming a heterodimeric complex known as cytochrome b558 (Cyt b558)58. NADPH oxidase activation requires translocation of cytosolic factors to the Nox2/p22phox complex and the present working model functions in the following way (Fig. 4): First, phosphorylation of p47phox leads to a conformational change allowing its interaction with p22phox. It is thought that p47phox organizes the translocation of other cytosolic factors, hence its designation as “organizer subunit.” The relocalization of p47phox to the membrane brings the “activator subunit” p67phox into contact with Nox2 and also brings the small subunit p40phox to the complex. Finally, the GTPase Rac interacts with Nox2 via a two-step mechanism involving an initial direct interaction with Nox2, followed by a subsequent interaction with p67phox. Once assembled, the complex is active and generates superoxide by transferring an electron from NADPH in the cytosol to oxygen on the luminal or extracellular space59.

24a diss.png

Fig. 4 - Assembly of the phagocyte NADPH oxidase Nox2. Nox2 and p22phox are found primarily in the membrane of intracellular vesicles. Upon activation, there is an exchange of GDP for GTP on Rac leading to its activation. Phosphorylation of the cytosolic p47phox subunit leads to conformational changes allowing interaction with p22phox. The movement of p47phox brings with it the other cytoplasmic subunits, p67phox and p40phox, to form the active Nox2 enzyme complex. Once activated, there is a fusion of Nox2-containing vesicles with the plasma membrane or the phagosomal membrane. The active enzyme complex transports electrons from cytoplasmic NADPH to extracellular or phagosomal oxygen to generate superoxide57


57. Roos D, Bruggena Rv, Meischl C. Oxidative killing of microbes by neutrophils. Microbes and Infection. 2003;5:1307-1315.

58. Thannickal VJ, Fanburg BL. Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol. 2000;279:L1005-1028.

59. Bedard K, Krause K-H. The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology. Physiol. Rev. 2007;87:245-313.

The activation of NOX2 occurs through a complex series of protein/protein interactions (Fig. 2; for more detailed recent reviews, see Refs. 328, 652, 844). NOX2 constitutively associates with p22phox. [...] Activation of NOX2 requires translocation of cytosolic factors to the NOX2/p22phox complex (Fig. 3). The present working model is as follows. Phosphorylation of p47phox leads to a conformational change allowing its interaction with p22phox(327, 843). It is thought that p47phox organizes the translocation

[page 250]


24a source.png

FIG. 3. Assembly of the phagocyte NADPH oxidase NOX2. [...] In resting neutrophil granulocytes, NOX2 and p22phox are found primarily in the membrane of intracellular vesicles. They exist in close association, costabilizing one another. Upon activation, there is an exchange of GDP for GTP on Rac leading to its activation. Phosphorylation of the cytosolic p47phox subunit leads to conformational changes allowing interaction with p22phox. The movement of p47phox brings with it the other cytoplasmic subunits, p67phox and p40phox, to form the active NOX2 enzyme complex. Once activated, there is a fusion of NOX2-containing vesicles with the plasma membrane or the phagosomal membrane. The active enzyme complex transports electrons from cytoplasmic NADPH to extracellular or phagosomal oxygen to generate superoxide (O2-).

of other cytosolic factors, hence its designation as “organizer subunit.” The localization of p47phox to the membrane brings the “activator subunit” p67phox into contact with NOX2 (342) and also brings the small subunit p40phox to the complex. Finally, the GTPase Rac interacts with NOX2 via a two-step mechanism involving an initial direct interaction with NOX2 (214), followed by a subsequent interaction with p67phox (476, 508). Once assembled, the complex is active and generates superoxide by transferring an electron from NADPH in the cytosol to oxygen on the luminal or extracellular space.


[...]

Anmerkungen

The source is given once, but it is not clear that so much text and in particular the illustration are taken from it.

The image is taken via copy-paste without reference. The source given, Roos et al. (2003), does not contain any of the copied material.

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(Hindemith), WiseWoman

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