Biomedical subjects

S Shida

Publications and source records attributed to S Shida.

At least 19 recordsLinked to original sources

PubMed2001

A dual signaling cascade that regulates the ectodomain shedding of heparin-binding epidermal growth factor-like growth factor.

Ectodomain shedding is an important mechanism to regulate the biological activities of membrane proteins. We focus here on the signaling mechanism of the ectodomain shedding of heparin-binding epidermal growth factor (EGF)-like growth factor (pro HB-EGF). Lysophosphatidic acid (LPA), a ligand for seven-transmembrane G protein-coupled receptors, stimulates the shedding of pro HB-EGF, which constitutes a G protein-coupled receptor-mediated transactivation of the EGF receptor. Experiments using a series of inhibitors and overexpression of mutant forms of signaling molecules revealed that the Ras-Raf-MEK signal is essential for the LPA-induced shedding. In addition, the small GTPase Rac is involved in the LPA-induced shedding, possibly to promote MEK activation. 12-O-Tetradecanoylphorbol-13-acetate is another potent inducer of pro HB-EGF shedding. We also demonstrate that the LPA-induced pathway is distinct from the 12-O-tetradecanoylphorbol-13-acetate-induced pathway and that these pathways constitute a dual signaling cascade that regulates the shedding of pro HB-EGF.

Androstadienes↗

PubMed2001

[Review of papers on the efficacy of the treatment in sudden deafness reported between 1989 and 1998 in Japan].

We reviewed hearing recovery in 3,430 patients with sudden deafness reported between 1989 and 1998 in Japan, evaluated using standards of the Research Group on Sudden Deafness of the Ministry of Health and Welfare of Japan. Complete recovery was seen in 30.8%, marked in 24.7%, slight in 23.3% and no change in 21.8%. No remarked improvement in recovery of hearing was seen in patients with sudden deafness in these 10 years. The number of patients studied in evaluating the efficacy of therapies may thus affect results. Complete recovery from sudden deafness was nearly 30% in proportion to the increase of number of patients studied in the literature. At least 200 patients should be studied to make a reliable evaluation.

Hearing Loss, Sudden↗

PubMed2000

Identification of mammalian TOM22 as a subunit of the preprotein translocase of the mitochondrial outer membrane.

A mitochondrial outer membrane protein of approximately 22 kDa (1C9-2) was purified from Vero cells assessing immunoreactivity with a monoclonal antibody, and the cDNA was cloned based on the partial amino acid sequence of the trypsin-digested fragments. 1C9-2 had 19-20% sequence identity to fungal Tom22, a component of the preprotein translocase of the outer membrane (the TOM complex) with receptor and organizer functions. Despite such a low sequence identity, both shared a remarkable structural similarity in the hydrophobicity profile, membrane topology in the Ncyt-Cin orientation through a transmembrane domain in the middle of the molecule, and the abundant acidic amino acid residues in the N-terminal domain. The antibodies against 1C9-2 inhibited the import of a matrix-targeted preprotein into isolated mitochondria. Blue native polyacrylamide gel electrophoresis of digitonin-solubilized outer membranes revealed that 1C9-2 is firmly associated with TOM40 in the approximately 400-kDa complex, with a size and composition similar to those of the fungal TOM core complex. Furthermore, 1C9-2 complemented the defects of growth and mitochondrial protein import in Deltatom22 yeast cells. Taken together, these results demonstrate that 1C9-2 is a functional homologue of fungal Tom22 and functions as a component of the TOM complex.

Adenosine Triphosphatases↗

PubMed2000

Domain analysis of the tetraspanins: studies of CD9/CD63 chimeric molecules on subcellular localization and upregulation activity for diphtheria toxin binding.

CD9 and CD63 belong to a tetramembrane-spanning glycoprotein family called tetraspanin, and are involved in a wide variety of cellular processes, but the structure-function relationship of this family of proteins has yet to be clarified. CD9 associates with diphtheria toxin receptor (DTR), which is identical to the membrane-anchored form of heparin-binding EGF-like growth factor (proHB-EGF). CD9 upregulates the diphtheria toxin (DT) binding activity of DTR/proHB-EGF, while CD63 does not upregulate the DT binding activity in spite of the fact that this protein also associates with DTR/proHB-EGF on the cell surface. CD9 molecules localize on the cell surface, while those of CD63 localize predominantly at lysosomes and intracellular compartments. We made CD9/CD63 chimeric molecules and then studied their intracellular localization and upregulation activities. The C-terminal regions of CD63, which includes the lysosome sorting motif, showed a strong inhibitory effect on the expression of the chimeric proteins at the cell surface, while mutants lacking the lysosome sorting motif delivered more efficiently on the cell surface, indicating that the lysosome sorting motif contributes to the inhibitory effect of the C-terminal region. However, the N-terminal half of this family of proteins containing the 1st to 3rd transmembrane domains also seems to influence the cell surface expression. For the upregulation of DT binding activity the large extracellular loop (EC2) of CD9 was essential, while the remaining regions influenced the upregulation activity by changing the efficiency of cell surface expression. From these results we discussed the structure-function relationship of this family of proteins.

Animals↗

PubMed1996

Familial occurrence of electrocardiographic abnormalities of the Brugada-type.

Electrocardiographic abnormalities were pointed out in a 51-year-old Japanese male whose major complaint was dizziness. His electrocardiogram showed a complete right bundle branch block, and a prolonged His bundle-ventricle (HV) interval of 100 msec. Two members of his family died of heart disease and 3 members, including a case of sudden death, presented an abnormal electrocardiogram of the Brugada-type with persistent ST segment elevation in the right precordial leads and right bundle branch block. The signal-averaged examination was made in the children of cases that died with the diagnosis of sudden death. Four cases showed a tendency of delay in the HV interval and a positive finding in the late potential. Further studies are necessary to clarify the relationship between electrocardiographic abnormalities of the Brugada-type and atrioventricular conduction disorder as well as to clarify the genetic basis of this disorder.

Adolescent↗

PubMed1994

Beta 1 adrenoceptor mediated decrease in pHi in quiescent ventricular myocardium.

OBJECTIVE: The aims were to examine the effect of beta adrenergic stimulation on the intracellular pH (pHi) and to compare it with that of alpha adrenergic stimulation in ventricular myocardium. METHODS: Using conventional and ion selective electrodes membrane potential and pHi were measured simultaneously in quiescent papillary muscles of guinea pigs in HEPES or bicarbonate buffered solution. Isoprenaline and propranolol (1 microM) plus phenylephrine (30 microM) were used to stimulate beta and alpha adrenoceptors, respectively. In order to evaluate underlying mechanism(s) of beta adrenoceptor mediated pHi change, effects of Na(+)-H+ exchange, Cl(-)-HCO3- exchange, Na(+)-HCO3- symport, and glycolysis blockers on the pHi change were examined. RESULTS: Isoprenaline (1 microM) produced a decrease in pHi of 0.08(SEM 0.01) pH units and a transient depolarisation of the resting membrane. The isoprenaline induced intracellular acidosis was blocked by the beta 1 blocker atenolol (10 microM) but not by the beta 2 blocker ICI 118,551 (0.1 microM). Forskolin also produced a decrease in pHi of 0.06(0.03) pH units. In contrast, alpha adrenergic stimulation produced an increase in pHi, which was abolished by 1 mM amiloride, an Na(+)-H+ exchange blocker. In the presence of amiloride, the isoprenaline induced decrease in pHi was rather enhanced. 4,4'-Diisothiocyanostilbene-2,2'-disulphonic acid (DIDS, 1 mM), a blocker of Cl(-)-HCO3- exchange and the Na(+)-HCO3- symport system, failed to affect the isoprenaline induced pHi decrease in bicarbonate buffered solution. However, pretreatment with 2-deoxyglucose or iodoacetic acid abolished the isoprenaline induced pHi decrease. CONCLUSIONS: beta 1 Adrenoceptor stimulation causes intracellular acidosis via the enhanced glycolysis, and the Na(+)-H+ exchange system appears to play a compensatory role. The beta 1 adrenoceptor mediated intracellular acidosis may modulate inotropic response to adrenergic stimulation in ventricular myocardium.

Adrenergic beta-Antagonists↗

PubMed1994