Three modes of age-related changes of hydrolytic enzymes in murine brain.

We followed the time course of the activities of various hydrolytic enzymes in murine brain for 30 months to investigate their roles in the aging process. Although most of the 15 enzymatic activities tested tended to rise with the increase in age, by analyzing them by multivariate analysis their movements could be divided into three types, each having a particular mode of nonlinear regression: exponential, logarithmic, or parabolic. Several enzymatic activities, including those of angiotensin-converting enzyme, esterase, trypsin-like enzyme, post-proline-cleaving enzyme, and Gly-Pro-aminopeptidase, showed rhythmic oscillations with about one cycle per 3 months throughout the period of 30 months.

The dissociation between the plasma levels of aminopeptidases A and B in spontaneously hypertensive rats.

We performed a longitudinal study for 20 weeks on spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKR) to determine the relationship between peptide metabolism and the age-dependent increase in blood pressure. In both SHR and WKR, the plasma level of aminopeptidase A (AP-A) clearly showed an age-dependent decrease. The plasma level of aminopeptidase B paralleled that of AP-A in WKR, but such an age-dependency was not observed in SHR, thus showing a dissociation between the two aminopeptidases.

Effects of 12-o-tetradecanoylphorbol-13-acetate and polyprenoic acid derivative on calcium-activated phospholipid-dependent protein kinase of pig skin.

12-o-Tetradecanoylphorbol-13-acetate (TPA) activates calcium-activated, phospholipid-dependent protein kinase (protein kinase C) partially purified in an ion exchange column from pig epidermis. Protein kinase C was activated by TPA in a concentration-dependent manner with simultaneous addition of Ca2+ and phospholipid. Polyprenoic acid derivative (E5166) which is a newly synthesized retinoic acid derivative, inhibited the TPA activation of protein kinase C.

A novel synthetic vitamin-A-like compound (a polyprenoic acid derivative: E-5166) inhibits UVB-stimulated epidermal ornithine decarboxylase activity.

Irradiation of skin with ultraviolet B (UVB) stimulates epidermal activity of ornithine decarboxylase (ODC), a rate limiting polyamine biosynthesing enzyme. The maximum stimulation of ODC activity by UVB was found at 24 after irradiation. Systemic administration of a polyprenoic acid derivative (E-5166) significantly inhibited the UVB-stimulated ODC activity in a dose-dependent manner.

Phosphorylation of soluble pig epidermal proteins by endogenous calcium-activated, phospholipid-dependent protein kinase.

Endogenous calcium-activated, phospholipid-dependent protein kinase phosphorylates pig epidermal protein. Pig epidermis was homogenized and centrifuged at 30,000 X g for 30 min. The supernatant was incubated with or without calcium and phospholipid.

Bestatin, a microbial aminopeptidase inhibitor, inhibits DNA synthesis induced by insulin or epidermal growth factor in primary cultured rat hepatocytes.

Bestatin, a microbial aminopeptidase inhibitor, inhibited insulin- or epidermal growth factor-induced DNA synthesis and cell proliferation in primary cultured hepatocytes of rats. The aminopeptidase inhibitor also affected the growth of FM3A or LOBN cells of mice, when it is included in the culture media at the concentration of 0.5 mg/ml.

Influence of angiotensin-converting enzyme inhibitor, foroxymithine, on dynamic equilibrium around the renin-angiotensin system in vivo.

To understand the in vivo actions of angiotensin-converting enzyme (ACE) inhibitors, a prolonged study was performed in rabbits over a half year, using one of such inhibitors, foroxymithine. During the initial 2 months of the inhibitor administration, the serum level of ACE was suppressed. Thereafter, probably triggered by the consequent sharp rise in the plasma renin activity (PRA) level, the ACE level regained its initial value.

Dissociation of creatine kinase activity from hydrolytic enzyme activities in muscle of dystrophic mice.

Time course studies were done to reexamine the age-dependency of intramuscular enzymatic changes in dystrophic mice. Most of the activities of hydrolytic enzymes in dystrophic mice were elevated in comparison to the controls throughout the span of 8 weeks which was examined. In contrast, the activity of creatine kinase remained depressed throughout the same period.

Abnormality of the post-proline-cleaving enzyme activity in mice with systemic lupus erythematosus-like syndrome.

Previous studies indicated the importance of hydrolytic enzymes in the pathogenesis of autoimmune diseases. In the present study, we examined the activities of such enzymes in various organs of the hybrids of the New Zealand Black and New Zealand White mouse (NZB/W mouse) as a laboratory model of human systemic lupus erythematosus. Of the 18 enzymatic activities tested, the activities of the post-proline-cleaving enzyme showed a particular behavior in the spleen of NZB/W mouse.

Relation of blood glucose levels to the changes in plasma levels of various hydrolytic enzymes in diabetic patients.

Plasma levels of various hydrolytic enzymes in diabetic patients, as diagnosed by their blood glucose levels, were compared with those of control subjects. Most of the levels of the aminopeptidase activities examined were significantly increased, while those of angiotensin-converting enzyme (ACE) and esterase decreased, in diabetic patients. The results of multivariate analysis suggest that the increased aminopeptidase activities are related rather to secondary organ lesions than to the primary pancreatic lesion.

Effect of esterastin, an acid lipase inhibitor, on the free and esterified cholesterol contents of cultured aortic smooth muscle cells treated with LDL and cholesterol ester liquid crystals.

The effects of esterastin, an acid lipase inhibitor, on the free and esterified cholesterol contents of cultured smooth muscle cells from pig aorta were examined. The post-nuclear supernatant fraction of the cell homogenate showed maximum acid cholesterol esterase activity at pH 4.5, and 50% of this activity was inhibited by 0.

Characterization of adenosine deaminase from normal human epidermis and squamous cell carcinoma of the skin.

We compared the characteristics of adenosine deaminases (ADs) (E.C. 3.

Epidermal growth factor stimulates release of arachidonic acid in pig epidermis.

Epidermal growth factor (EGF) at physiologic concentrations (0.001-0.1 microgram/ml) stimulated the release of [14C] arachidonic acid [14C-AA] from pig epidermis.

Epidermal growth factor stimulates tyrosine phosphorylation of pig epidermal fibrous keratin.

Epidermal growth factor (EGF) stimulated phosphorylation of pig epidermal proteins, one of which was pig epidermal keratin. In order to further characterize phosphorylated proteins and specify the EGF-dependent protein phosphorylation, we attempted to identify phosphorylated keratin proteins and to analyze phosphorylated phosphoamino acids of keratin proteins stimulated by EGF. Four major polypeptide bands of pig epidermal keratin were immunoprecipitated by antihuman callus keratin antibody which reacted with fine networks of fibrous keratin of pig epidermal cells grown in vitro.

Systemic changes in hydrolytic enzyme activities in mice affected with murine leprosy.

In order to investigate the behavior of hydrolytic enzymes in chronic infections, the activities of 17 hydrolytic enzymes were tested in limb muscles, heart muscle, spleen, liver, and kidney of lepromatous mice infected with Mycobacterium lepraemurium (M. lepraemurium) and their controls. Typical increases in those enzymatic activities were seen in spleen and liver, where pathological changes were the most pronounced, especially at the 11th week after the inoculation of the bacilli.