Contribution of PKC to beta-hexosaminidase-induced airway smooth muscle proliferation.
beta-Hexosaminidases (Hex) A and B promote mitogenesis via airway smooth muscle (ASM) mannose receptor. The objective of this study was to elucidate the contribution of protein kinase C (PKC) in Hex-induced mitogenesis in ASM cells (ASMC). Exposure of ASMC to Hex caused increases in both the calcium-dependent and the calcium-independent PKC activities. Both downregulation of PKC and PKC inhibitors staurosporine and calphostin C diminished Hex-induced DNA synthesis and cell number. Hex-induced DNA synthesis was enhanced by a diacylglycerol kinase inhibitor, R-59022, which was blocked by calphostin C. These data suggest that activation of PKC in part mediates Hex-induced mitogenesis in ASMC.
Lew
D B
DB
Department of Pediatrics, College of Medicine, University of Tennessee, Memphis 38103, USA.
Brown
E R
ER
Dempsey
B K
BK
Wright
H M
HM
Malik
K U
KU
D000818:Animals; D002417:Cattle; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D019852:Diacylglycerol Kinase; D004791:Enzyme Inhibitors / Q000494:pharmacology; D054818:Hexosaminidase A; D007328:Insulin / Q000494:pharmacology; D009130:Muscle, Smooth / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009281:Naphthalenes / Q000494:pharmacology; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D011744:Pyrimidinones / Q000494:pharmacology; D011994:Recombinant Proteins; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014132:Trachea / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D007328:Insulin; D009281:Naphthalenes; D010982:Platelet-Derived Growth Factor; D011744:Pyrimidinones; D011994:Recombinant Proteins; D013844:Thiazoles; C095477:platelet-derived growth factor AB; D010660:Phenylisopropyladenosine; C047505:R 59022; D017853:Phosphotransferases (Alcohol Group Acceptor); D019852:Diacylglycerol Kinase; D011493:Protein Kinase C; D054818:Hexosaminidase A; D001619:beta-N-Acetylhexosaminidases; D019311:Staurosporine; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine