Kumamoto University

About: Kumamoto University is a education organization based out in Kumamoto, Kumamoto, Japan. It is known for research contribution in the topics: Population & Cancer. The organization has 19602 authors who have published 35513 publications receiving 901260 citations. The organization is also known as: Kumamoto Daigaku.

Aldosterone Induces Angiotensin-Converting-Enzyme Gene Expression in Cultured Neonatal Rat Cardiocytes

Abstract: Background — The cardiac renin-angiotensin-aldosterone system is activated in failing hearts in proportion to the severity of the disease. We hypothesized that a positive feedback mechanism might exist within this system and contribute to the progression of the heart failure. Methods and Results — To test this hypothesis, we examined whether angiotensin II or aldosterone induces the expression of angiotensin-converting-enzyme (ACE) mRNA in cultured neonatal rat ventricular cardiocytes. Expression of ACE mRNA was detected and quantified using real-time reverse transcription-polymerase chain reaction. Exposure to angiotensin II (10−5 mol/L) for 24 hours had no significant effect on the expression of ACE mRNA (0.7±0.5-fold versus control, P =NS), but similar treatment with aldosterone (10−5 mol/L) induced a 23.3±7.9-fold increase ( P <0.01) in ACE mRNA expression. The effect of aldosterone was both time- (maximal effect, 24 hours) and dose-dependent (EC50, 4×10−7 mol/L), and it was significantly ( P <0.01) inhibited by spironolactone, a specific mineralocorticoid receptor antagonist. Conclusions — Aldosterone upregulates ACE mRNA expression, which is blocked by spironolactone in neonatal rat cardiocytes. Thus, spironolactone may suppress the progression of heart failure by blocking the effects of aldosterone and angiotensin II. Received February 23, 2001; revision received May 1, 2001; accepted May 15, 2001.

Protein S-guanylation by the biological signal 8-nitroguanosine 3′,5′-cyclic monophosphate

Abstract: The signaling pathway of nitric oxide (NO) depends mainly on guanosine 3',5'-cyclic monophosphate (cGMP). Here we report the formation and chemical biology of a nitrated derivative of cGMP, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), in NO-mediated signal transduction. Immunocytochemistry demonstrated marked 8-nitro-cGMP production in various cultured cells in an NO-dependent manner. This finding was confirmed by HPLC plus electrochemical detection and tandem mass spectrometry. 8-Nitro-cGMP activated cGMP-dependent protein kinase and showed unique redox-active properties independent of cGMP activity. Formation of protein Cys-cGMP adducts by 8-nitro-cGMP was identified as a new post-translational modification, which we call protein S-guanylation. 8-Nitro-cGMP seems to regulate the redox-sensor signaling protein Keap1, via S-guanylation of the highly nucleophilic cysteine sulfhydryls of Keap1. This study reveals 8-nitro-cGMP to be a second messenger of NO and sheds light on new areas of the physiology and chemical biology of signal transduction by NO.

Role of Pax‐5 in the regulation of a mid‐hindbrain organizer’s activity

Abstract: The mes-metencephalic boundary (isthmus) has been suggested to act as an organizer in the development of the optic tectum. Pax-5 was cloned as a candidate for regulator of the organizing center. Isthmus-specific expression of Pax-5 and analogy with the genetic cascade in Drosophila suggest that Pax-5 may be at a higher hierarchical position in the gene regulation cascade of tectum development. To examine this possibility, a gain-of-function experiment on Pax-5 was carried out. In ovo electroporation on E2 chick brain with the eucaryotic expression vector that encodes chick Pax-5 cDNA was used. Not only was a considerable amount of Pax-5 expressed ectopically in the transfected brain, but irregular bulging of the neuroepithelium was induced in the diencephalon and mesencephalon. At Pax-5 misexpressing sites, uptake of BrdU was increased. Histological examination of E7 transfected brain revealed that Pax-5 caused transdifferentiation of diencephalon into the tectum-like structure. In the bulges of the E7 mesencephalon, differentiation of laminar structure was repressed when compared to the normal side. In transfected embryos, En-2, Wnt-1 and Fgf8 were up-regulated ectopically, and Otx2 was down-regulated in the diencephalon to mesencephalon. Moreover, Ephrin-A2, which is expressed specifically in the tectum with a gradient highest at the caudal end, is suggested to be involved in pathfinding of the retinal fibers, and was induced in the bulges. When the mouse Fgf8 expression vector was electroporated, Pax-5 and chick Fgf8 were also induced ectopically. These results suggest that Pax-5, together with Fgf8, hold a higher position in the genetic hierarchy of the isthmus organizing center and regulate its activity.

Modulation of enhanced vascular permeability in tumors by a bradykinin antagonist, a cyclooxygenase inhibitor, and a nitric oxide scavenger

Abstract: The mechanism of the enhanced vascular permeability and retention (EPR) effect seen in solid tumors was investigated with sarcoma 180 (S-180) in mice by using the bradykinin receptor antagonist d-Arg-[Hyp3,Thi5,d-Tic7,Oic8]bradykinin] (HOE 140), the nitric oxide (NO) scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO), and the cyclooxygenase (prostaglandin synthase) inhibitor indomethacin. In the S-180 solid tumor model, administration of HOE 140 (0.65 or 1.3 µg/kg/8 h, s.c.), PTIO (167 mg/kg/2 h, four times/8 h, i.p.), or indomethacin (5 or 10 mg/kg/day, three times, i.p.) significantly suppressed the EPR effect in the tumor, and the combined administration of these agents achieved a stronger inhibition of the EPR effect than did each compound alone. Indomethacin (10 mg/kg/day, three times) plus PTIO (167 mg/kg/2 h, four times) given i.p. had the greatest inhibition (70%) on the EPR effect. When HOE 140 was administered s.c. at a dose of 13 µg/kg/12 h for 2 weeks after tumor inoculation, growth of the solid tumor was also suppressed by 32%, by tumor weight. In the ascitic form of S-180, i.p. administration of HOE 140 at 13 µg/kg/12 h initiated immediately after tumor inoculation significantly suppressed formation of S-180 tumor ascites; the life span of ascitic S-180 tumor-bearing mice was prolonged at the same dose of HOE 140. The expression of inducible NO synthase mRNA and of cyclooxygenase 2 mRNA in S-180 tumor tissue was highly elevated, as evidenced by Northern blotting and reverse transcription-PCR and by Southern blot analyses. These results indicate that bradykinin, NO, and prostaglandins play an important role in enhanced vascular permeability in tumor tissue and sustain tumor growth. More importantly, bradykinin antagonists such as HOE 140 may be beneficial for the inhibition of tumor growth.

Simple Photoreduction of Graphene Oxide Nanosheet under Mild Conditions

Abstract: Graphene oxide (GO) nanosheets were reduced by UV irradiation in H2 or N2 under mild conditions (at room temperature) without a photocatalyst. Photoreduction proceeded even in an aqueous suspension of nanosheets. The GO nanosheets reduced by this method were analyzed by X-ray photoelectron spectroscopy and Raman spectroscopy. It was found that epoxy groups attached to the interiors of aromatic domains of the GO nanosheet were destroyed during UV irradiation to form relatively large sp2 islands resulting in a high conductivity. I−V curves were measured by conductive atomic force microscopy (AFM; perpendicular to a single nanosheet) and a two-electrode system (parallel to the nanosheet). They revealed that photoreduced GO nanosheets have high conductivities, whereas nonreduced GO nanosheets are nearly insulating. Ag+ adsorbed on GO nanosheets promoted the photoreduction. This photoreduction method was very useful for photopatterning a conducting section of micrometer size on insulating GO. The developed pho...