Hemolysate induces tyrosine phosphorylation and collagen-lattice compaction in cultured fibroblasts.
Hemolysate, a proposed causative agent for cerebral vasospasm after subarachnoid hemorrhage, produces contraction of cerebral arteries by activation of tyrosine kinases. In addition, hemolysate increases fibroblast-collagen compaction that could play a role in cerebral vasospasm. We studied the effect of hemolysate on tyrosine phosphorylation and fibroblast-collagen compaction in cultured canine basilar and human dermal fibroblasts using tyrosine kinase inhibitors and tyrosine antibodies. Hemolysate enhanced tyrosine phosphorylation of two proteins, 64 and 120 kDa, in cultured canine basilar artery and human dermal fibroblast cells. The effect of hemolysate was time-dependent and concentration-dependent. Oxyhemoglobin and ATP, the two major components of hemolysate, produced similar tyrosine phosphorylation, however, with a different time course. Tyrosine kinase inhibitors genistein and tyrphostin A51 abolished the effect of hemolysate in both cerebral and dermal fibroblasts. Hemolysate increased fibroblast-populated collagen-lattice compaction and tyrosine kinase inhibitors genistein and tyrphostin A51 attenuated the effect of hemolysate. We conclude that hemolysate activates tyrosine kinase that leads to the increase of fibroblast compaction. This effect of hemolysate may contribute to cerebral vasospasm.
Patlolla
A
A
Department of Neurosurgery, University of Mississippi Medical Center, Jackson, Mississippi, 39216, USA.
Ogihara
K
K
Aoki
K
K
Zubkov
A
A
Bengten
E
E
Parent
A D
AD
Zhang
J H
JH
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry* / Q000502:physiology; D004285:Dogs; D005347:Fibroblasts / Q000378:metabolism* / Q000502:physiology; D006461:Hemolysis; D006801:Humans; D010108:Oxyhemoglobins / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D014443:Tyrosine / Q000378:metabolism*; D020301:Vasospasm, Intracranial / Q000209:etiology
D010108:Oxyhemoglobins; D014443:Tyrosine; D000255:Adenosine Triphosphate; D003094:Collagen; D011505:Protein-Tyrosine Kinases