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Biomedical subjects

T Aoyagi

Publications and source records attributed to T Aoyagi.

At least 361 records · Page 20Linked to original sources
PubMed1984

Different enzymatic oscillations in vivo caused by the stereoisomers of an aminopeptidase inhibitor, bestatin.

The present study was undertaken to compare the enzymatic oscillations induced in three major organs, spleen, kidney, and liver, of mice by the active and inactive forms of an aminopeptidase inhibitor, bestatin. Although bestatin caused sine curve-type oscillations of enzymatic activities in spleen and kidney, its isomer, possessing no enzyme-inhibiting actions and no biological actions, did not show any typical enzymatic changes. Such typical oscillations were not elicited by either one of those two agents in liver, in spite of the apparent difference in the type of oscillations induced by them in this organ. These observations were taken to indicate that the enzymatic oscillations in vivo caused by bestatin are closely related to its aminopeptidase-inhibiting actions seen in vitro and that the immunomodifying actions of this agent are based on its effects on enzymes sensitive to it, possibly involving immunoresponsive cells.

Aminopeptidases↗
PubMed1984

In vivo actions of bestatin-related compounds in relation to their actions in vitro.

A study was performed to elucidate the effects of low-molecular-weight enzyme inhibitors on enzyme networks in vivo. Seven compounds, including bestatin and its 5 derivatives and arphamenine B, were tested, with each of them being administered to mice at the dose of 200 micrograms/day for 8 consecutive days. The spectrum of enzymatic changes thus induced were extensive and were not simply explainable by the in vitro actions of each agent administered. Nevertheless, a multivariate study on the changes in enzyme networks showed some degree of interrelationship between the in vitro and in vivo actions of the agents under study. The present findings seem to certify that the direct enzyme-inhibiting effect motivates the extensive movement of enzyme networks in vivo, although the latter often seems rather paradoxical at a glance.

Aminopeptidases↗
PubMed1983

Adenosine deaminase in human epidermis from healthy and psoriatic subjects.

Adenosine deaminase, which catalyzes the irreversible hydrolytic deamination of adenosine and deoxyadenosine to inosine and deoxyinosine respectively, plays an important role in the degradation of adenine nucleotide and purine nucleotide salvage pathway metabolism. We investigated human epidermal adenosine deaminase activity using a radiochemical method, which enabled us to measure the adenosine deaminase activity of protein samples as small as several micrograms. We measured adenosine deaminase activity of microdissected pure epidermis of the healthy skin and the psoriatic affected and unaffected skin. It was shown that psoriatic affected epidermis had increased adenosine deaminase activity compared with the healthy epidermis (P less than 0.05) and the unaffected epidermis (P less than 0.01). There was no difference in enzyme activity between healthy and psoriatic unaffected epidermis. The increased adenosine deaminase activity in the psoriatic affected epidermis may reflect the accelerated salvage pathway of the nucleic acid metabolism probably associated with the hyperproliferative condition of the psoriatic epidermis.

Adenosine Deaminase↗
PubMed1983

Two different modes of enzymatic changes in serum with progression of Duchenne muscular dystrophy.

Nineteen serum enzymes from patients with Duchenne muscular dystrophy and asthma, and normal subjects were studied. These enzymes include aminopeptidases, cathepsin C, angiotensin-converting enzyme, serine proteinase, sulphatase, phosphatase, esterases and ribonuclease. The enzymatic changes in dystrophic patients were related to two parameters: severity of the disease as judged from symptomatology, and duration of the disease. Most of the enzyme levels tested were increased in milder cases, but they tended to decrease with severity of the disease. On the other hand, there was a group of enzymes showing just opposite tendencies: serine proteinase, cathepsin C and ribonuclease. Even when viewed from the relationship to duration of the disease, the above mentioned grouping of enzymes was generally valid. Most of the enzyme levels, including those routinely applied as clinical parameters, tended to decrease, logarithmically, with an increase in duration of the disease. On the contrary, some others, including serine proteinase, cathepsin C and ribonuclease, tended to increase toward their control levels. Such tendencies were not found in the patients with asthma. The discrepancy between the above two groups of enzymes may have some implications for the process of protein degradation in dystrophic patients.

Adolescent↗
PubMed1983

Enzymatic changes in dystrophic mice and their age dependency.

The activities of 14 different aminopeptidases, 5 endopeptidases, 4 glycosidases, phosphatase, esterase, and ribonuclease (RNase) were measured in the muscle and bone of 12 normal controls and 12 dystrophic mice. In most cases the activity of these enzymes was significantly elevated in the muscle of the dystrophic mice. In the muscle of the controls the activity of aminopeptidase A (AP-A), Leu-AP, Trp-AP, Gly-Pro-AP, and RNase tended to decrease with the increasing age of the animal, whereas that of AP-B and Pro-AP tended to increase. This mode of age-related regression was entirely different in dystrophic muscle. The enzymatic changes in the bone of the dystrophic mice were milder but more or less analogous to those in muscle. These findings should be important in further elucidating the mode of protein degradation in dystrophic muscle and in aiding in the selection of appropriate therapeutic agents including the low-molecular-weight inhibitors.

Aging↗
PubMed1983

Esterastin: a potent inhibitor of lysosomal acid lipase.

The effect of a fungal metabolite, esterastin, on lysosomal acid lipase purified from rabbit liver was studied. Esterastin inhibited the enzyme activity very strongly (IC50, about 80 nM). The inhibition of acid lipase by esterastin was competitive with respect to the substrate and the inhibition constant for esterastin was 90 nM. Esterastin was less inhibitory to other lipolytic enzymes, such as pancreatic lipase and carboxylesterase. Thus esterastin is a potent new inhibitor of lysosomal acid lipase.

Animals↗
PubMed1983

Phospholipase A2 activity modulates "ischemic effect" in pig skin.

The level of cyclic AMP in the epidermis rapidly increase within 15 min after separation from the in vivo condition. This phenomenon is the so-called "ischemic effect." In order to elucidate the possible mechanism of the ischemic effect, the effects of melittin and mepacrine on the ischemic condition of the skin were studied. Melittin, a stimulator of phospholipase A2, lessened the increase of cyclic AMP, while mepacrine, an inhibitor of phospholipase A2, potentiated the increase of cyclic AMP during the ischemic condition. The overall results suggest that phospholipase A2 may play an important role in the induction of the ischemic condition through membrane alteration.

Animals↗
PubMed1983

Epidermal growth factor stimulates phosphorylation of pig epidermal keratin protein.

Endogenous protein phosphorylation of pig epidermis by epidermal growth factor (EGF) was studied to elucidate biologic roles of EGF on epidermal cells. EGF stimulated phosphorylation of keratin proteins (Mr: 65,000, 60,000, 56,000, and 51,000) identified by the Ouchterlony immunodiffusion analysis, a low Mr protein (16,000 dalton) of the urea-SDS-mercaptoethanol soluble fraction, and a 30,000 dalton Tris-HCl soluble protein. The phosphorylated epidermal proteins such as keratin proteins and a 30,000 dalton protein of the Tris-HCl soluble fraction were slightly dephosphorylated following the addition of unlabeled phosphate. Anti-EGF serum eliminated the EGF-stimulated phosphorylation of keratin proteins, a low Mr protein, and a 30,000 dalton Tris-HCl soluble protein. The overall results indicate that EGF specifically stimulated phosphorylation of several epidermal proteins, one of which was keratin protein.

Animals↗
PubMed1983

Relation between in vivo effects and in vitro effects of serine and thiol proteinase inhibitors.

In the present study we investigated the relationship between the in vivo effects and the in vitro effects of serine and thiol proteinase inhibitors. Each one of the inhibitors, leupeptin, dansyl-L-leucyl-L-argininal (Dan-Leu-Argal), pyroglutamyl-L-leucyl-L-argininal (Pyr-Leu-Argal), E-64C or EP-459 was given intraperitoneally to mice for 8 consecutive days and various enzymatic activities were tested in 6 organs: forelimb muscle, hindlimb muscle, heart, spleen, liver and kidney. A multivariate analysis clearly differentiated the effects of leupeptin from those of its two analogues (Dan-Leu-Argal and Pyr-Leu-Argal), while the two analogues showed close relations with each other as to their in vivo effects. E-64C and EP-459 also showed resemblance of in vivo effects between them, but the effects of these two agents were clearly differentiated from those of leupeptin and its two analogues. This kind of study seems important to assess the in vivo effects of physiologically active substances including enzyme inhibitors.

Animals↗
PubMed1983

Systemic enzymatic changes in guinea pigs suffering from experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) is one of the experimental models of human demyelinating diseases and recently is regarded also as a useful model for studying cell-mediated autoimmune diseases. Because of the possibility of induction of systemic changes in this model, we investigated enzymatic changes in serum and main organs of the diseases animals, including brain, spinal cord, limb muscle, heart muscle, spleen, liver and kidney. The enzymes measured consisted of 7 aminopeptidases, 5 endopeptidases, 3 glycosidases, creatine kinase, phosphatase and esterase. Significant changes of many enzymatic activities occurred in all the organs tested in 1 to 2 weeks after the administration of EAE antigen, myelin basic protein (MBP). Interesting correlations of the pattern of enzymatic changes were seen among most of the organs tested. Those patterns changed in the course of the 2 weeks and there remained marked changes characteristic for each organ. This model may represent some type of systemic autoimmune diseases.

Animals↗
PubMed1983

Enzymatic changes in various organs of guinea pigs caused by the administration of Freund's complete adjuvant.

Although our previous studies demonstrated marked changes in the activities of hydrolytic enzymes in guinea pigs afflicted with experimental allergic encephalomyelitis (EAE), it is possible that at least some parts of them were due to the effects of Freund's complete adjuvant (FCA) per se used for immunization. Thus we tried to find the property of the enzymatic changes in the tissues of limb muscle, heart muscle, spleen, liver, kidney, brain, spinal cord and serum induced by the administration of FCA alone to the guinea pigs. FCA caused rather intensive enzymatic changes in every organ tested. When the patterns of these enzymatic changes were compared with those of the animals afflicted with EAE, a significant correlation was seen only in forelimb muscle at 1 week after the injection of the agents, whereas at 2 weeks significant correlations were seen in heart and liver. Although these results indicate that in some organs there are some similarities between the two experimental conditions, the degree of determination for this phenomenon was not high, being 28% at the highest. This means that most of the enzymatic changes seen in the animals afflicted with EAE could not be explained by the effects of FCA. It was concluded that FCA causes unique and systemic enzymatic changes when administered to the animals.

Animals↗