Time filter

Source Type

Ishida Y.-I.,Meiji Pharmaceutical University | Yamasaki M.,University of Miyazaki | Yukizaki C.,Miyazaki Prefecture Food Research and Development Center | Nishiyama K.,University of Miyazaki | And 4 more authors.
Human Cell | Year: 2014

Adult T-cell leukemia/lymphoma (ATL) is a fatal malignancy caused by infection with human T-lymphotropic virus type-1 and there is no accepted curative therapy for ATL. We searched for biological active substances for the prevention and treatment of ATL from several species of herbs. The ATL cell growth-inhibitory activity and apoptosis assay showed that carnosol, which is an ingredient contained in rosemary (Rosmarinus officinalis), induced apoptosis in ATL cells. Next, to investigate the apoptosis-inducing mechanism of carnosol, we applied proteomic analysis using fluorescent two-dimensional differential gel electrophoresis and mass spectrometry. The proteomic analysis showed that the expression of reductases, enzymes in glycolytic pathway, and enzymes in pentose phosphate pathway was increased in carnosol-treated cells, compared with untreated cells. These results suggested that carnosol affected the redox status in the cells. Further, the quantitative analysis of glutathione, which plays the central role for the maintenance of intracellular redox status, indicated that carnosol caused the decrease of glutathione in the cells. Further, N-acetyl-l-cystein, which is precursor of glutathione, canceled the efficiency of carnosol. From these results, it was suggested that the apoptosis-inducing activity of carnosol in ATL cells was caused by the depletion of glutathione. © 2013 Japan Human Cell Society and Springer Japan.

Miyazaki Prefectural Industrial Support Foundation and University of Miyazaki | Date: 2010-03-26

Provided is a preventive, progression inhibitor or remedy for a disease one of the causes of which is the activation of the P13K/AKT signaling pathway or vice versa. A phosphorylation-inhibiting and/or dephosphorylating agent, which has an effect of inhibiting the phosphorylation at least at one of the phosphorylation sites of PTEN protein selected from the group consisting of T382, T383 and S380 and/or an effect of dephosphorylating the same, is prepared. Alternatively, a phosphorylation-inhibiting or dephosphorylating agent for PTEN is screened by a method comprising a step for confirming an ability of a test substance to inhibit the phosphorylation at least at one of the phosphorylation sites of PTEN protein selected from the group consisting of T382, T383 and S380 or a dephosphorylation ability thereof. Then, a substance having an effect opposite to the inhibition of PTEN phosphorylation or dephosphorylation thereof, e.g., an antibody against the phosphorylation-inhibiting or dephosphorylating agent for PTEN obtained above, is also obtained.

Mera K.,Kagoshima University | Uto H.,Kagoshima University | Mawatari S.,Kagoshima University | Ido A.,Kagoshima University | And 12 more authors.
BMC Gastroenterology | Year: 2014

Background: Apoptosis inhibitor of macrophage (AIM) and adipocytokines are involved in the metabolic syndrome, which has been putatively associated with the progression of chronic hepatitis C (CHC). However, the association between these cytokines and CHC is not fully elucidated. The aim of this study is to test whether serum levels of AIM and adipocytokines are associated with histological features, homeostasis model assessment-insulin resistance index (HOMA-IR), or whole body insulin sensitivity index (WBISI) in CHC patients.Methods: Serum samples were obtained from 77 patients with biopsy-proven CHC. In 39 patients without overt diabetes mellitus, a 75 g oral glucose tolerance test (OGTT) was performed and HOMA-IR and WBISI were calculated.Results: A serum AIM level of ≥1.2 μg/ml was independently associated with advanced hepatic fibrosis (F2 or F3) (odds ratio [OR], 5.612; 95% confidence interval [CI], 1.103-28.563; P = 0.038) based on a multivariate analysis, but there was no significant association between AIM and hepatic steatosis or inflammation. Furthermore, a serum leptin level of ≥8.6 ng/ml was independently associated with the presence of hepatic steatosis (≥5%) (OR, 6.195; 95% CI, 1.409-27.240; P = 0.016), but not hepatic fibrosis or inflammation. No relationship was observed between levels of adiponectin or resistin and hepatic histological parameters based on a multivariate analysis. Although serum levels of leptin, resistin, and adiponectin were significantly correlated with HOMA-IR and WBISI, there was no significant relationship between serum AIM levels and HOMA-IR or WBISI, respectively.Conclusion: High serum levels of AIM in CHC patients are potentially related to advanced hepatic fibrosis. AIM and adipocytokines are possibly associated with pathological changes via a different mechanism. © 2014 Mera et al.; licensee BioMed Central Ltd.

Tsuruda T.,University of Miyazaki | Hatakeyama K.,University of Miyazaki | Nagamachi S.,University of Miyazaki | Sekita Y.,University of Miyazaki | And 10 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2012

Objective-The mechanisms underlying abdominal aortic aneurysm development remain unknown. We hypothesized that acceleration of glucose metabolism with the upregulation of glucose transporters is associated with abdominal aortic aneurysm development. Methods and Results-Enhanced accumulation of the modified glucose analogue 18 fluoro-deoxyglucose by positron emission tomography imaging in the human abdominal aortic aneurysm was associated with protein expressions of glucose transporters-1 and-3, assessed by Western blot. The magnitude of glucose transporter-3 expression was correlated with zymographic matrix metalloproteinase-9 activity. Intraperitoneal administration of glycolysis inhibitor with 2-deoxyglucose significantly attenuated the dilatation of abdominal aorta induced by periaortic application of CaCl 2 in C57BL/6J male mice or reduced the aneurysmal formation in angiotensin II-infused apolipoprotein E knockout male mice. In monocytic cell line induced by phorbol 12-myristate 13-acetate or ex vivo culture obtained from human aneurysmal tissues, 2-deoxyglucose abrogated the matrix metalloproteinase-9 activity and interleukin-6 expression in these cells/tissues. Moreover, 2-deoxyglucose attenuated the survival/proliferation of monocytes and the adherence of them to vascular endothelial cells. Conclusion-This study suggests that the enhanced glycolytic activity in aortic wall contributes to the pathogenesis of aneurysm development. In addition, pharmacological intervention in glycolytic activity might be a potential therapeutic target for the disorder. © 2012 American Heart Association, Inc.

Mawatari S.,Kagoshima University | Uto H.,Kagoshima University | Ido A.,Kagoshima University | Nakashima K.,Hamamatsu University School of Medicine | And 12 more authors.
PLoS ONE | Year: 2013

Background: It has been hypothesized that persistent hepatitis C virus (HCV) infection is mediated in part by viral proteins that abrogate the host immune response, including the complement system, but the precise mechanisms are not well understood. We investigated whether HCV proteins are involved in the fragmentation of complement component 4 (C4), composed of subunits C4α, C4β, and C4γ, and the role of HCV proteins in complement activation. Methods: Human C4 was incubated with HCV nonstructural (NS) 3/4A protease, core, or NS5. Samples were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and then subjected to peptide sequencing. The activity of the classical complement pathway was examined using an erythrocyte hemolysis assay. The cleavage pattern of C4 in NS3/4A-expressing and HCV-infected cells, respectively, was also examined. Results: HCV NS3/4A protease cleaved C4γ in a concentration-dependent manner, but viral core and NS5 did not. A specific inhibitor of NS3/4A protease reduced C4γ cleavage. NS3/4A protease-mediated cleavage of C4 inhibited classical pathway activation, which was abrogated by a NS3/4A protease inhibitor. In addition, co-transfection of cells with C4 and wild-type NS3/4A, but not a catalytic-site mutant of NS3/4A, produced cleaved C4γ fragments. Such C4 processing, with a concomitant reduction in levels of full-length C4γ, was also observed in HCV-infected cells expressing C4. Conclusions: C4 is a novel cellular substrate of the HCV NS3/4A protease. Understanding disturbances in the complement system mediated by NS3/4A protease may provide new insights into the mechanisms underlying persistent HCV infection. © 2013 Mawatari et al.

Discover hidden collaborations