17Beta-estradiol induces gastrointestinal motility disorder by decreasing CPI-17 phosphorylation via changes in rho-family G-protein Rnd expression in small intestine
| Autor: | Masatoshi Hori, Aya Shimomura, Takashi Ohama, Hiroshi Ozaki |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
RHOA Ovariectomy Motility Muscle Proteins Organ culture Tissue Culture Techniques Hsp27 In vivo GTP-Binding Proteins Ileum medicine Animals Phosphorylation Rats Wistar General Veterinary biology Dose-Response Relationship Drug Estradiol Rnd3 Muscle Smooth Phosphoproteins Small intestine Cell biology Rats medicine.anatomical_structure Biochemistry Gene Expression Regulation biology.protein Carbachol Female Gastrointestinal Motility Muscle Contraction |
| Zdroj: | The Journal of veterinary medical science. 71(12) |
| ISSN: | 0916-7250 |
| Popis: | In the present study, we investigated the long-term effects of 17beta-estradiol on the motility of small intestine in in vitro organ culture and in vivo treatment studies. When rat ileal circular smooth muscle tissues were cultured with 17beta-estradiol (0.1 and 1 microM) for 5 days, carbachol-induced contraction was inhibited. In ileal tissue isolated from ovariectomized rat treated with 17beta-estradiol (200 microg/kg/day s.c. for 3 days), carbachol-induced contraction was also impaired. Both in vitro and in vivo, 17beta-estradiol treatment upregulated heat shock protein 27 (HSP27) expression, indicating the activation of estrogen receptor in the intestinal smooth muscle. 17beta-estradiol did not change protein expression levels of RhoA and RhoA-associated coiled coil-forming serine/threonine kinases (ROCKs); however, it upregulated Rnd2 and Rnd3, Rho-family G-proteins that counteract the functions of RhoA, both in vitro and in vivo. In organ culture, treatment of ileal tissue with 17beta-estradiol greatly suppressed the carbachol-induced increase in phosphorylation at Thr38 in CPI-17 without altering total CPI-17 protein expression. These results suggest that 17beta-estradiol upregulates Rnd expression to inhibit the RhoA-mediated Ca(2+) sensitization of contractile mechanisms, which are mediated by CPI-17 phosphorylation in ileal smooth muscle. This mechanism may contribute to the intestinal motility disorder occurring in gender-dependent bowel diseases. |
| Databáze: | OpenAIRE |
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