Possible role of the protein kinase C/CPI-17 pathway in the augmented contraction of human myometrium after gestation.
| Autor: | Ozaki, Hiroshi, Yasuda, katsuhiko, Kim, Yoon-Sun, Egawa, Makoto, Kanzaki, Hideharu, Nakazawa, Hiroshi, Hori, Masatoshi, Seto, Minoru, Karaki, Hideaki |
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| Předmět: |
PROTEIN kinase C
PHORBOLS UTERINE contraction PHOSPHATASES PREGNANCY PREGNANT women MYOSIN IMMUNOBLOTTING CALCIUM metabolism RNA metabolism MUSCLE protein metabolism SERINE metabolism CARCINOGENS COMPARATIVE studies ENZYME inhibitors ENZYMES ESTERASES HETEROCYCLIC compounds INORGANIC compounds ISOENZYMES RESEARCH methodology MEDICAL cooperation MUSCLE contraction MUSCLE proteins MYOMETRIUM PHOSPHOPROTEINS PHOSPHORYLATION THIRD trimester of pregnancy RESEARCH TRANSFERASES WESTERN immunoblotting EVALUATION research INDOLE compounds CHEMICAL inhibitors PHARMACODYNAMICS PHYSIOLOGY |
| Zdroj: | British Journal of Pharmacology; Dec2003, Vol. 140 Issue 7, p1303-1312, 10p, 1 Diagram, 9 Graphs |
| Abstrakt: | 1 Activation of protein kinase C (PkC) by phorbol 12.13-dibulylate (PDBu, 1 μM ) induced sustained contractions with no increase in [Ca[sup2+]][subi] in nonpregnant and pregnant human myometria The contractile effects of PDBu in pregnant myometrium were much greater than those in nonpregnant myometrium, and the contractions in pregnant myometrium were accompanied by an increase in myosin light chain (MLC) phosphorylation at Ser[sup19]. 2 The contraction induced by PDBu in pregnant myometrium was inhibited by the inhibitors of conventional PKC isoforms. bisindolylmaleimides and indolocarbazole. such as Go6976. Go6983.and Go6850 (1 μM) LY333531Y3 (1μM),a specific inhibitor of PKCβ also inhibited the he PDBu-induced contraction in the pregnant myometrium. 3 In the pregnant rnyometriurn permeabilized with atoxin. PDBu increased the contract ions induced, at fixed Ca[sup2+] concentration (0.3μM) both in nonpregnant and pregnant myometrai. indicating Ca[sup2+] sensitization of contractile elements. 4 Western immunoblot analysis indicated that pregnant myometrium contained PKC isozymes such as conventional PKC (αβγ),novel PKC (δ, ε, ϑ), and atpical PKC (ζ but not t λ). RT-PCR and real-time RT-PCR analysis indicated that among the conventional PKC. the levels of mRNA of β isoform in pregnant human myometruim were greater than those in nonpregnant myometrium. 5 CPI-17 is a substrate for PKC. and the phosphorylated CPI-17 is considered to inhibit myosin phosphatase. The levels of CPI-17 mRNA and protein expression were also greater in the pregnant myometrium. 6 The results suggest that the PKC-mediated contractile mechanism is augmented in human myometrium after gestation. and that this augmentation may he attributable to the increased activity of the β PKC isoform and CPI-17. [ABSTRACT FROM AUTHOR] |
| Databáze: | Complementary Index |
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