Significance of heme oxygenase in prolactin-mediated cell proliferation and angiogenesis in human endothelial cells.
Our objectives were to determine whether heme oxygenase-1 is a second messenger for prolactin-mediated angiogenesis. Endothelial cell proliferation and angiogenesis assay demonstrated that cell number and capillary formation were increased by prolactin (10 and 25 ng/ml). Both protein synthesis and mRNA analysis confirmed that HO-1 expression was induced by prolactin in cultured endothelial cells and occurred in a concentration-dependent manner. Endothelial cells transduced with retrovirus-mediated delivery of HO-1 gene in sense and antisense orientation were used to further determine whether HO-1 overexpression or underexpression modulated prolactin-mediated endothelial cell proliferation and angiogenesis. Incubation of human microvessel endothelial cells transduced with HO-1 in sense orientation resulted in enhancement of prolactin-mediated increase in endothelial cell proliferation and angiogenesis, whereas inhibition of HO-1 by transduction of HO-1 in antisense orientation prevented prolactin increase in endothelial cell proliferation. Similarly, addition of stannic mesoporphyrin, the inhibitor of HO activity, prevented PRL-mediated increase in endothelial cell proliferation. Our results demonstrated for the first time, that prolactin-mediated angiogenesis and cell proliferation was dependent on HO-1 gene expression.
Malaguarnera
Lucia
L
Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA.
Pilastro
Maria Rosaria
MR
Quan
Shuo
S
Ghattas
Maivel H
MH
Yang
Liming
L
Mezentsev
Alexandre V
AV
Kushida
Taketoshi
T
Abraham
Nader G
NG
Kappas
Attalah
A
D002455:Cell Division / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005822:Genetic Vectors; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D009389:Neovascularization, Pathologic / Q000201:enzymology*; D011388:Prolactin / Q000494:pharmacology*; D012190:Retroviridae
D011388:Prolactin; D006419:Heme Oxygenase (Decyclizing)