RESUMEN
The article Laxative effect of repeated Daiokanzoto is attributable to decrease in aquaporin-3 expression in the colon, written by Risako Kon, Miho Yamamura, Yukari Matsunaga, Hiroshi Kimura, Moe Minami, Saki Kato, Nobutomo Ikarashi, Kiyoshi Sugiyama, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 27 January 2018 without open access.
RESUMEN
Daiokanzoto (DKT) exerts its laxative effect via colonic inflammation caused by sennoside A in Daio (rhubarb). Previously, we showed that the laxative effect of sennoside A is related to decreased aquaporin-3 (AQP3) expression in mucosal epithelial cells due to colonic inflammation. We also found that a combination of glycyrrhizin, an ingredient in Kanzo (glycyrrhiza), and sennoside A attenuates the inflammatory response induced by sennoside A and reduces its laxative effect. These findings indicate that DKT may be a long-term treatment for chronic constipation, but there is no evidence supporting this hypothesis. In this study, we analyzed the laxative effect of repeated DKT administration, focusing on AQP3 expression in the colon. After rats were treated for 7 days, decreased AQP3 expression and the onset of diarrhea were observed in the DKT group, but were not seen in the Daio group either. Although the relative abundance of gut microbiota after repeated DKT administration was similar to that after control treatment, Daio reduced Lactobacillaceae, Bifidobacteriaceae, and Bacteroidaceae levels and markedly increased Lachnospiraceae levels. In this study, we show that DKT has a sustained laxative effect, even upon repeated use, probably because it maintains decreased AQP3 expression and gut microbiota homeostasis. This outcome therefore indicates that DKT can be used as a long-term treatment for chronic constipation.
Asunto(s)
Acuaporina 3/metabolismo , Colon/efectos de los fármacos , Laxativos/uso terapéutico , Extractos Vegetales/uso terapéutico , Animales , Glycyrrhiza uralensis , Laxativos/farmacología , Masculino , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , RhusRESUMEN
While irinotecan (CPT-11) has a potent anti-cancer effect, it also causes serious diarrhea as an adverse reaction. In this study, we analyzed the pathogenic mechanism of CPT-11-induced delayed diarrhea by focusing on water channel aquaporin-3 (AQP3) in the colon. When rats received CPT-11, the expression level of AQP3 was reduced during severe diarrhea. It was found that the expression levels of inflammatory cytokines and the loss of crypt cells were increased in the colon when CPT-11 was administered. When celecoxib, an anti-inflammatory drug, was concomitantly administered, both the diarrhea and the reduced expression of AQP3 induced by CPT-11 were suppressed. The inflammation in the rat colon during diarrhea was caused via activated macrophage by CPT-11. These results showed that when CPT-11 is administered, the expression level of AQP3 in the colon is reduced, resulting in delayed diarrhea by preventing water transport from the intestinal tract. It was also suggested that the reduced expression of AQP3 might be due to the inflammation that occurs following the loss of colonic crypt cells and to the damage caused by the direct activation of macrophages by CPT-11. Therefore, it was considered that anti-inflammatory drugs that suppress the reduction of AQP3 expression could prevent CPT-11-induced delayed diarrhea.
Asunto(s)
Acuaporina 3/metabolismo , Camptotecina/análogos & derivados , Colon/metabolismo , Diarrea/prevención & control , Animales , Acuaporina 3/genética , Acuaporina 4/genética , Acuaporina 4/metabolismo , Acuaporinas/genética , Acuaporinas/metabolismo , Camptotecina/farmacología , Camptotecina/uso terapéutico , Celecoxib/farmacología , Supervivencia Celular/efectos de los fármacos , Colon/efectos de los fármacos , Colon/patología , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Citocinas/genética , Citocinas/metabolismo , Diarrea/patología , Diarrea/veterinaria , Heces/química , Expresión Génica/efectos de los fármacos , Irinotecán , Masculino , Ratones , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Células RAW 264.7 , Ratas , Ratas WistarRESUMEN
Pleurotus ostreatus was transformed using the nourseothricin-resistant gene for the first time. The transformation efficiency was 1.3±0.6transformants/µg plasmid DNA. In addition, the transformation efficiency of the bialaphos-resistant gene was increased to 26.7±11.5transformants/µg plasmid DNA.
Asunto(s)
ADN de Hongos/genética , Pleurotus/genética , Transformación Genética , Antifúngicos/farmacología , Farmacorresistencia Fúngica/genética , Marcadores Genéticos , Compuestos Organofosforados/farmacología , Plásmidos , Pleurotus/efectos de los fármacos , Estreptotricinas/farmacologíaRESUMEN
The subcellular localization of 13 recently identified N-myristoylated proteins and the effects of overexpression of these proteins on cellular morphology were examined with the aim of understanding the physiological roles of the protein N-myristoylation that occurs on these proteins. Immunofluorescence staining of HEK293T cells transfected with cDNAs coding for the proteins revealed that most of them were associated with the plasma membrane or the membranes of intracellular compartments, and did not affect cellular morphology. However, two proteins, formin-like2 (FMNL2) and formin-like3 (FMNL3), both of them are members of the formin family of proteins, were associated mainly with the plasma membrane and induced significant cellular morphological changes. Inhibition of protein N-myristoylation by replacement of Gly2 with Ala or by the use of N-myristoylation inhibitor significantly inhibited membrane localization and the induction of cellular morphological changes, indicating that protein N-myristoylation plays critical roles in the cellular morphological changes induced by FMNL2 and FMNL3.
