Functional role of PKC in contraction of cultured human prostatic stromal cells.
The contractile activity of prostatic stromal cells contributes to symptoms of benign prostatic hyperplasia (BPH). However, the mechanisms for this contraction have not yet been fully elucidated. In this study, we investigated the role of protein kinase C (PKC) in prostatic contraction by measuring the isometric tension development of cultured human prostatic stromal cells (CHPSCs) derived from BPH patients. Fresh human BPH tissue was used only in a Western blot analysis. A ring preparation made of CHPSCs and collagen gel could develop an isometric tension during activation with various agonists. Phorbol 12,13 dibutyrate (PDBu), a PKC activator, induced a relaxation. A Western blot analysis revealed the expression of PKC-potentiated protein phosphatase-1 inhibitory protein (CPI-17) in both CHPSCs and fresh human BPH tissue to be much lower than that in the rabbit aorta. When CPI-17 was over-expressed, PDBu induced a large contraction, but the agonist-induced contraction did not become larger than expected. In alpha-toxin permeabilized preparations, PDBu induced a relaxation in control CHPSCs, while it induced a contraction at a constant [Ca2+]i in CPI-17 over-expressing CHPSCs. These results indicated that the activation of PKC in CHPSCs induces a relaxation probably due to low expression level of CPI-17 and also that the PKC-CPI-17 pathway does not appear to play a major role in the agonist-induced contraction even when CPI-17 was over-expressed.
Takahashi
Ryosuke
R
Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Japan.
Nishimura
Junji
J
Hirano
Katsuya
K
Naito
Seiji
S
Kanaide
Hideo
H
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology; D002478:Cells, Cultured; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D009124:Muscle Proteins; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000096:biosynthesis / Q000235:genetics; D011467:Prostate / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D011470:Prostatic Hyperplasia / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology*; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D017154:Stromal Cells / Q000187:drug effects / Q000201:enzymology; D010738:Type C Phospholipases / Q000378:metabolism
D001426:Bacterial Proteins; D002273:Carcinogens; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D009124:Muscle Proteins; C107507:PPP1R14A protein, human; D011993:Recombinant Fusion Proteins; C054562:yellow fluorescent protein, Bacteria; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases; D010738:Type C Phospholipases; D002118:Calcium