Disulfide-linked and transglutaminase-catalyzed protein assemblies in platelets.
Energy depletion induces the formation of disulfide-linked and transglutaminase-catalyzed protein assemblies in platelets. The disulfide type polymers, formed following incubation at 37 degrees C in the absence of adenosine triphosphate (ATP)-generating precursors, are composed of cytoskeletal proteins and are associated with a decrease of reduced glutathione levels accompanying ATP depletion. The maintenance of ATP and reduced glutathione levels to, respectively, 34% and 47% of their original values is sufficient to prevent the formation of both polymer types. The transglutaminase-type cross-links are formed in the presence of calcium in either "energy-depleted" or thrombin stimulated platelets. 125I-surface-labeled membrane proteins, presumably transmembrane proteins, are incorporated into the transglutaminase-catalyzed cross-linked polymer of thrombin-stimulated platelets. Glycoproteins IIb and IIIa are not essential to the polymer formation, since thrombasthenic platelets treated with thrombin exhibit the same type of labeled polymer. The transglutaminase-catalyzed polymer formation following thrombin stimulation of platelets is inhibited by a calcium channel blocker, an intracellular calcium antagonist, as well as other inhibitors such as indomethacin, dibutyryl cyclic AMP, and prostaglandin E1. Although the evidence points to the formation of transglutaminase-catalyzed cross-linking in the cytoplasmic compartment, additional cross-linking of extruded components cannot be excluded.
Cohen
I
I
Lim
C T
CT
Kahn
D R
DR
Glaser
T
T
Gerrard
J M
JM
White
J G
JG
D000217:Acyltransferases / Q000097:blood; D000227:Adenine Nucleotides / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism* / Q000648:ultrastructure; D001798:Blood Proteins / Q000378:metabolism*; D002118:Calcium / Q000097:blood; D003598:Cytoskeletal Proteins / Q000097:blood* / Q000378:metabolism; D004220:Disulfides; D004734:Energy Metabolism; D005176:Factor XIII / Q000378:metabolism; D005978:Glutathione / Q000097:blood; D006801:Humans; D007526:Isoelectric Point; D008970:Molecular Weight; D011108:Polymers; D013917:Thrombin; D011503:Transglutaminases
D000227:Adenine Nucleotides; D001798:Blood Proteins; D003598:Cytoskeletal Proteins; D004220:Disulfides; D011108:Polymers; D005176:Factor XIII; D000217:Acyltransferases; D011503:Transglutaminases; D013917:Thrombin; D005978:Glutathione; D002118:Calcium