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Biomedical subjects

J F Kuo

Publications and source records attributed to J F Kuo.

At least 127 records · Page 7Linked to original sources
PubMed1981

Changes in cyclic nucleotide levels and phosphodiesterase and protein kinase activities in mitogenically stimulated 3T3 fibroblasts.

Activities of cyclic-nucleotide-hydrolysing enzymes cAMP-, cCMP- and cGMP phosphodiesterase, the intracellular concentrations of cAMP, cCMP, and cGMP, and the activity of the cAMP-dependent protein kinase were studied in serum-starved 3T3 cells stimulated to proliferate by serum. Within 1 and 2 min after stimulation the activities of cAMP- and cGMP phosphodiesterase were unaffected while the concentration of cGMP was raised and that of cAMP lowered, suggesting increased synthesis of cGMP and simultaneously reduced synthesis of cAMP. 48 h after stimulation, when the cells multiplied rapidly, both the cAMP phosphodiesterase and the cCMP phosphodiesterase were reduced. Evidence was also obtained that cAMP-dependent protein kinase is important for expressing the cAMP effect in the 3T3 cells.

Animals↗
PubMed1981

Substrate proteins for calmodulin-sensitive and phospholipid-sensitive Ca2+-dependent protein kinases in heart, and inhibition of their phosphorylation by palmitoylcarnitine.

At least two substrate proteins for phospholipid-sensitive Ca2+-dependent protein kinase and at least six substrates for calmodulin-sensitive Ca2+-dependent protein kinase were identified in the cytosol of the guinea pig heart. In the particulate subfractions enriched in nuclei, mitochondria, microsome, or plasma membrane, no substrates for the phospholipid-sensitive enzyme were demonstrated but at least four substrates for the calmodulin-sensitive enzyme were identified. The present studies suggest that phospholipid, acting independently of calmodulin, is likely to be involved in the regulation of Ca2+-dependent protein phosphorylation in the heart. Phosphorylation of endogenous substrates for the two enzyme systems was effectively inhibited by palmitoylcarnitine. When histone was used as exogenous substrate, the carnitine ester inhibited the cardiac phospholipid-sensitive Ca2+-dependent protein kinase but not the cardiac cyclic AMP-dependent and cyclic GMP-dependent protein kinases. It is suggested that inhibition of the Ca2+-dependent phosphorylation of cardiac proteins, regulated by either phospholipid or calmodulin, is probably related in part to the great increase in this fatty acid metabolic intermediate in the ischemic heart.

Animals↗
PubMed1980

Stimulation by phosphatidylserine and calmodulin of calcium-dependent phosphorylation of endogenous proteins from cerebral cortex.

The Ca2+-dependent phosphorylation of a number of proteins in the cytosol of the rat or guinea pig cerebral cortex was profoundly stimulated by phosphatidylserine; calmodulin, on the other hand, had only a minimal effect. The Ca2+-dependent phosphorylation of different proteins from the total particulate fraction of the same tissue, in comparison, was specifically stimulated by either phosphatidylserine or calmodulin. The present findings, in line with the phospholipid-sensitive Ca2+-dependent protein kinase recently recognized, suggest an involvement of phospholipid in regulating Ca2+-dependent phosphorylation of endogenous substrate proteins. This new system presumably functions independent or in a complementary manner with the calmodulin-sensitive Ca2+-dependent protein phosphorylation system previously reported by others.

Animals↗
PubMed1980

Calcium-dependent protein kinase: widespread occurrence in various tissues and phyla of the animal kingdom and comparison of effects of phospholipid, calmodulin, and trifluoperazine.

A widespread occurrence of Ca2+-dependent protein kinase was shown in various tissues and phyla of the animal kingdom. Phosphatidylserine appeared to be more effective than calmodulin in supporting the Ca2+-dependent phosphotransferase activity. The phospholipid-sensitive Ca2+-dependent protein kinase activity, distributed in both the cytosolic and particulate fractions, was not inhibited by trifluoperazine, a specific inhibitor of calmodulin-sensitive, Ca2+-dependent reactions or processes. The enzyme activity levels, compared to those of cyclic AMP-dependent and cyclic GMP-dependent protein kinases, were exceedingly high in certain tissues (such as brain and spleen) and exhibited a much greater disparity among tissues. The Ka for Ca2+ was about 100 microM in the presence of phosphatidylserine; the value was as low as 2 microM in the presence of phosphatidylserine and diolein. It is suggested that phospholipid-sensitive Ca2+-dependent protein kinase may mediate certain actions of Ca2+ in tissues, acting independently or in a complementary manner with other protein phosphorylation systems stimulated by calmodulin-Ca2+, cyclic AMP, or cyclic GMP.

Animals↗
PubMed1980

Thyroxine-induced changes in characteristics and activities of beta-adrenergic receptors and adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate systems in the heart may be related to reputed catecholamine supersensitivity in hyperthyroidism.

Modifications in characteristics and activities of beta-adrenergic receptors and certain parameters of the cyclic nucleotide systems were observed in the hypertrophied heart of the rat chronically treated with T4. These include: 1) an increased number of beta-adrenergic receptors without a change in their affinity, as determined by binding of (-)-[3H]dihydroalprenolol to the membrane; 2) increased sensitivity and magnitude of stimulation of adenylate cyclase in homogenates by isoproterenol, without a change in the basal or NaF-stimulated (total) enzyme activity; 3) decreased formation of cAMP and decreased activation of cAMP-dependent protein kinase in the minced heart stimulated by isoproterenol, probably due to decreased myocardial ATP concentration; 4) decreased activity of cAMP phosphodiesterase in the particulate fraction; 5) decreased activity of cGMP-dependent protein kinase in both the soluble and particulate fractions, accompanied by decreased activity of cAMP-dependent protein kinase in the particulate fraction; 6) decreased activity of the stimulatory modulator of cGMP-dependent protein kinase and, conversely, increased activity of the inhibitory modulator of cAMP-dependent protein kinase; and 7) increased sensitivity accompanied by decreased maximum tension development of the ventricular strip to contract in response to isoproterenol. These alterations largely disappeared upon regression of the hyperthyroid state. It is suggested that the above changes, many of which were the opposite of those reported earlier for the desensitized and hypertrophied rat heart caused by isoproterenol, may in part consitute the molecular basis for the reputed catecholamine supersensitivity of the heart in the hyperthyroid state.

Adenylyl Cyclases↗
PubMed1978

Alterations in activities of cyclic nucleotide systems and in beta-adrenergic receptor-mediated activation of cyclic AMP-dependent protein kinase during progression and regression of isoproterenol-induced cardiac hypertrophy.

Initial and transient increases in the basal levels of cyclic GMP in the heart were noted prior to cardiac hypertrophy in rats administered isoproterenol. Increased levels of cyclic AMP-phosphodiesterase (in both the soluble and particulate fractions) and stimulatory modulator of cyclic GMP-dependent protein kinase, however, were associated with the progression, or the state, of cardiomegaly, with their levels returning to the control values upon regression of the hypertrophy. The levels of cyclic GMP phosphodiesterase in the soluble fraction were lower, whereas those in the particulate fraction were higher, in the hypertrophied heart than the control. In cardiac hypertrophy, the maximal activity ratio(--cyclic AMP/+cyclic AMP) of cyclic AMP-dependent protein kinase in the incubated minced heart caused by isoproterenol was lower, whereas the concentration of isoproterenol required to increase the activity ratio half-maximally was higher than controls; the reduced responsiveness to the drug, however, was reversed when the hypertrophy regressed. These observations, taken collectively, appear to suggest that the desensitization of the beta-adrenergic mechanism seen in the cardiac hypertrophy produced by repeated administration of isoproterenol is associated with adaptive modifications in certain parameters of the cyclic nucleotide systems.

Animals↗
PubMed1978

Cytidine 3',5'-monophosphate phosphodiesterase: decreased activity in the regenerating and developing liver.

A decrease in the activity of the enzyme cytidine 3',5'-monophosphate (cyclic CMP) phosphodiesterase was noted in the regenerating liver of young rats as early as 8 hours after partial hepatectomy, with a maximum decrease occurring 12 hours after the surgery. In comparison, in old rats which showed a slower liver growth, the maximum decrease in the activity of cyclic CMP phosphodiesterase was smaller and occurred at a much later time (2 days after surgery). A similar decrease in the enzyme activity was observed in the fetal liver of guinea pigs. These findings suggest that regulation of tissue concentration of cyclic CMP may be crucial for the regeneration and development of the liver.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1978

Cytidine 3':5'-monophosphate phosphodiesterase in mammalian tissues. Occurrence and biological involvement.

A phosphodiesterase activity that preferentially hydrolyzed cytidine 3':5'-monophosphate was partially purified from rat liver extract. The enzyme was best activated by Fe2+ (5 to 10 mM). Mn2+ and Mg2+ were less effective, whereas Zn2+, Co2+, and Ca2+ were ineffective. It exhibited kinetics typical of a high Km phosphodiesterase, with a Km for cycli CMP of 2.4 mM. The enzyme, inhibited by theophylline and 1-methyl-3-isobutyl xanthine to much less extents than cyclic AMP and cyclic GMP phosphodiesterases, was found in all rat tissues examined, with highest levels seen in the liver, kidney, and intestine, and lowest levels found in the skeletal muscle, cerebellum, aorta, and blood cells. The enzyme levels in the regenerating liver were found to be about 40% lower than the control liver of rats; they were also 3 to 10 times lower in the fetal liver, lung, and heart than the corresponding adult tissues of guinea pigs. These findings suggest that depressed cyclic CMP phosphodiesterase may be in part related to cell proliferation, in line with reports that the regenerating liver has higher levels of cyclic CMP (Bloch, A. (1975) Adv. Cycli Nucleotide Res. 5, 331-338) and cytidylate cyclase (Cech, S. Y., and Ignarro, L.J. (1977) Science 198, 1063-1065).

Animals↗
PubMed1978

Depression of cytidine 3':5'-cyclic monophosphate phosphodiesterase activity in developing tissues of guinea pigs.

Changes in levels of the newly discovered cytidine 3':5'-cyclic monophosphate (cyclic CMP) phosphodiesterase in some representative tissues (cerebral cortex, kidney, intestine, liver, heart, and lung) of guinea pigs from various developmental stages (fetus, neonate, pup, and adult) were studied and compared with those of cyclic AMP and cyclic GMP phosphodiesterases in the same tissues. It was observed that the tissue levels of cyclic CMP phosphodiesterase were invariably the lowest in every one of the fetal tissues examined, the highest in the corresponding tissues from the pups and adult, with intermediate levels seen in some neonatal tissues. The patterns of the ontogenetic changes in levels of cyclic AMP and cyclic GMP phosphodiesterase activities, however, were variable and tissue specific. These findings suggest that the depressed cyclic CMP phosphodiesterase activity (hence, the elevated cyclic CMP concentration) is perhaps a common factor in developing tissues undergoing rapid cell proliferation. The data also suggest that metabolism of cyclic CMP is perhaps more closely related to cell proliferation than the metabolism of cyclic AMP or cyclic GMP.

Animals↗