Novel evidence of PLC delta2 involvement in the regulation of the differential evolution of human aneurysms.
The biological and molecular mechanisms which are responsible for the formation and possible evolution of human aneurysms are unknown. Previous investigations have pointed to the possible involvement of inositol specific-phospholipase C (PLC) in the mechanisms related to the formation or evolution of intracranial aneurysms, but, thus far, a relationship of one or more PLC isoforms with the biological signals influencing the fate of this lesion has not been demonstrated. The aim of this study was to investigate the expression, activity and possible modification of PLC isoforms in intracranial aneurysms in patients undergoing elective surgical repair after casual identification of unruptured aneurysms, or during emergency surgical repair of ruptured aneurysms. PLC and proliferating cell nuclear antigen (PCNA) expressions were detected by immunohistochemical analysis; PLC activity was obtained by measuring its hydrolytic activity on labelled PIP(2); PKC activity was measured by total kinase activity assay. Results indicated no substantial differences between controls and aneurysms, with the only exception being PLC delta2 which was nearly absent in controls and ruptured aneurysms, while strongly expressed and functionally active in almost all unruptured aneurysms. In addition, its expression always correlated with the proliferation cell marker PCNA, while its specific activity always correlated to PKC activity. PLC delta2 distribution, regulation and role in human tissues are still unknown Therefore, although preliminary, these data provide a novel insight into the signalling machinery influencing the aneurismal progression.
Section of Human Anatomy, Department of Biomorphology, University "G. D'Annunzio", Chieti-Pescara, Italy.
M
M
Marchisio
G M
GM
Sabatino
A
A
Albanese
E
E
Santavenere
R
R
Buonaguidi
S
S
Miscia
D000328:Adult; D000368:Aged; D017542:Aneurysm, Ruptured / Q000201:enzymology / Q000503:physiopathology / Q000601:surgery; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D018450:Disease Progression; D004632:Emergency Medical Services; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D002532:Intracranial Aneurysm / Q000201:enzymology* / Q000503:physiopathology* / Q000601:surgery; D007527:Isoenzymes / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D019635:Neurosurgical Procedures; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000502:physiology; D054803:Phospholipase C delta; D010738:Type C Phospholipases / Q000502:physiology*
D007527:Isoenzymes; D019269:Phosphatidylinositol 4,5-Diphosphate; D004247:DNA; D010738:Type C Phospholipases; D054803:Phospholipase C delta