Angiotensin II induces secretion of plasminogen activator inhibitor 1 and a tissue metalloprotease inhibitor-related protein from rat brain astrocytes.
The present study investigates angiotensin (Ang) II effects on secretory protein synthesis in brain astrocytes cultured from neonatal and 21-day-old rats. Ang II-induced changes in the de novo synthesis of [35S]methionine-labeled secretory proteins were visualized using two-dimensional NaDodSO4/PAGE. Astrocytes from 21-day-old rat brain possess specific high-affinity receptors for Ang II. These cells express two Ang II-induced secretory proteins with Mr 55,000 (AISP-55K) and Mr 30,000 (AISP-30K), which were time- and dose-dependent (EC50, 1 nM). [Sar1, Ile8]Ang II (where Sar is sarcosine) inhibited Ang II-induced secretion of AISP-55K but not AISP-30K. N-terminal amino acid sequencing indicates that AISP-55K is identical to rat plasminogen activator inhibitor 1, whereas AISP-30K exhibits 72-81% identity to three closely related proteins: human tissue inhibitor of metalloproteases, a rat phorbol ester-induced protein, and the murine growth-responsive protein 16C8. Immunofluorescent staining with rat plasminogen activator inhibitor 1 antibody was induced in the majority of cells in culture after Ang II treatment of astrocytes from 21-day-old rat brains. Absence of this response to Ang II in astrocytes from neonatal rat brain provides evidence that this action of Ang II on astrocytes is developmentally regulated.
Olson
J A
JA
Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville 32610.
Shiverick
K T
KT
Ogilvie
S
S
Buhi
W C
WC
Raizada
M K
MK
D000375:Aging; D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000254:growth & development / Q000502:physiology*; D002478:Cells, Cultured; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000096:biosynthesis*; D007700:Kinetics; D008715:Methionine / Q000378:metabolism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D015849:Plasminogen Inactivators / Q000378:metabolism*; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D013462:Sulfur Radioisotopes; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D009419:Nerve Tissue Proteins; D015849:Plasminogen Inactivators; D013462:Sulfur Radioisotopes; D019714:Tissue Inhibitor of Metalloproteinases; D000804:Angiotensin II; D008715:Methionine