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Biomedical subjects

C J Limas

Publications and source records attributed to C J Limas.

At least 91 records · Page 5Linked to original sources
PubMed1978

Enhanced phosphorylation of myocardial sarcoplasmic reticulum in experimental hyperthyroidism.

Calcium transport by cardiac sarcoplasmic reticulum (SR) was compared in hyperthyroid (HT) and euthyroid (ET) rats. Both Ca2+ uptake (97 +/- 3.1 nmol/mg per min in HT vs. 63 +/- 2.9 nmol/mg per min in ET, P less than 0.01) and CA2+ -stimulated ATPase activity (61 +/- 4.1 vs. 37 +/- 1.6 nmol Pi/mg per min, P less than 0.01) were higher in the thyroxine-treated animals. These changes were accompanied by enhanced cyclic AMP-dependent phosphorylation of cardiac SR in hyperthyroid rats (180 +/- 4.3 pmol Pi/mg per min vs. 117 +/- 4.2 pmol Pi/mg per min, P less than 0.01). SDS-polyacrylamide gel electrophoresis of cardiac SR showed that phosphorylation of a 22,000-dalton protein (phospholamban) primarily accounted for the differences between the two groups. There was no difference in the rate of SR dephosphorylation by endogenous phosphoprotein phosphatase between HT and ET rats. Differences in cyclic AMP-dependent phosphorylation between the two groups were blunted in the presence of excess exogenous cyclic AMP-dependent protein kinase. These results suggest that increased levels or activity of endogenous cyclic AMP-dependent protein kinases may partially explain enhanced calcium transport by the cardiac SR of hyperthyroid animals.

Animals↗
PubMed1978

Myocardial nuclear protein kinases during postnatal development.

Chromatin template activity of isolated rat myocardial cells declines progressively during the first few weeks of postnatal life, a time period also characterized by restriction in myocardial proliferative capacity. Multiple protein kinases have been isolated from the nuclei of myocardial cells. Protein kinase activity decreased progressively during the first 3 wk of postnatal development, mostly in two fractions (III and V). Cyclic AMP dependency, substrate specificity, and phosphorylation patterns of endogenous substrates did not change appreciably with age. Higher phosphorylating activity of protein kinases from younger rats correlated with increased capacity to enhance myocardial RNA synthesis in vitro. This suggests the possibility that the decrease in chromatin template activity with age may be, in part, related to the decline in nuclear phosphokinase activities.

Aging↗
PubMed1977

Adenosine 3',5'-monophosphate-dependent protein kinases of myocardial non-histone nuclear proteins.

Myocardial acidic non-histone nuclear proteins (NHPs) contain endogenous protein kinase activity. Phosphocellulose chromatography of purified NHPs identifies nine separate peaks of protein kinases which can phosphorylate both endogenous and exogenous substrates to a variable degree; endogenous NHPs are the best substrates. Cyclic AMP-stimulated protein kinase induced phosphorylation of endogenous and exogenous substrates; the extent of this stimulation varied according to the protein kinase fraction and substrate used. Cyclic AMP also enhanced NHP-induced stimulation of RNA polymerase activity. This enhancement was dependent on protein kinase-induced phosphorylation of NHPs since it was prevented by alkaline phosphatase pretreatment. It is concluded that nuclear protein kinases regulate myocardial RNA synthesis by enhancing phosphorylation of NHPs and that this regulation is under cyclic AMP control.

Adenosine Triphosphate↗
PubMed1977

Selective stimulation of venous prostaglandin E 9-ketoreductase by bradykinin.

The effects of bradykin on prostaglandin metabolism in canine mesenteric vessels were examined. Bradykinin stimulated microsomal prostaglandin synthesis in both artery and vein; this stimulation was more pronounced when [14C] hosphatidylcholine rather than [14C] arachidonate was used as the substrate for prostaglandin synthetase. This suggested that bradykinin enhanced a membrane phospholipase. In addition, bradykinin selectively stimulated prostaglandin E 9-ketoreductase activity from veins but not arteries. This may explain the finding that bradykinin induces the release of prostaglandin E compounds from arteries but prostaglandin F compounds from veins.

Alcohol Oxidoreductases↗
PubMed1977

Prostaglandin metabolism in the kidneys of spontaneously hypertensive rats.

Renal prostaglandins have been implicated in the regulation of blood pressure. We have therefore compared prostaglandin metabolism in the kidneys of spontaneously hypertensive rats (SHR's) of the Aoki-Okamoto strain and normotensive Wistar-Kyoto (WKY) controls. The microsomal fraction of the renal medulla contained most of the prostaglandin synthetase activity in both groups; SHR's had significantly higher enzymatic activity than their normotensive controls at age 10 wk and thereafter; furthermore, synthetase activity in SHR's increased with age. Two forms of 15-hydroxyprostaglandin dehydrogenases were demonstrated: an NAD+-dependent form which was localized mainly in the cortex and an NADP+-dependent form, higher in the medulla. The activities of these enzymes were lower in the hypertensive animals at all ages studied; this depression was more pronounced for the NAD+-dependent dehydrogenase. The results indicate that, in hypertension, renal prostaglandin metabolism is altered so that enhanced synthesis is accompanied by decreased degradation rate.

Aging↗
PubMed1977

Vascular prostaglandin synthesis in the spontaneously hypertensive rat.

Vascular prostaglandin synthesis was studied in tissues (aorta and inferior vena cava) obtained from spontaneously hypertensive rats (SHRs) of the Aoki-Okamoto strain and age-matched Wistar-Kyoto (WKYs) controls. PGE2 synthesis in aortas from SHRs was significantly enhanced at 10 wk of age (5.3 +/- 0.7 nmol PGE2/mg protein per 10 min vs. 1.9 +/- 0.03 nmol PGE2/mg protein per min in the WKYs, P less than 0.001) and increased progressively until 22 wk of age; PGE2alpha synthesis in SHRs was not significantly different from WKYs. In the venous walls from SHRs, PGF2alpha was the prostaglandin predominantly synthesized (7.1 +/- 0.6 vs. 1.9 +/- 0.05 nmol PGE2alpha/mg protein per 10 min in the WKY controls, P less than 0.01). The activities of 15-hydroxy prostaglandin dehydrogenase and PGE 9-ketoreductase were also compared in the two groups of animals. The only difference detected was a significant increase in venous PGE 9-ketoreductase of SHR's (7.3 +/- 0.06 vs. 4.8 +/- 0.04 nmol PGF2alpha/mg per min, P less than 0.01). The results suggest that increased vascular synthesis of prostaglandins accompanies the development of spontaneous hypertension and may serve to attenuate the effects of blood pressure elevation.

Aging↗
PubMed1977

Defective calcium transport by cardiac sarcoplasmic reticulum in spontaneously hypertensive rats.

Ca2+ uptake and binding and Ca2+-ATPase activity of cardiac sarcoplasmic reticulum (SR) from spontaneously hypertensive rats (SHR) were compared to that obtained from normotensive Wistar-Kyoto (WKY) rats. Ca2+ uptake (172 +/- 3.7 nmol/mg of protein per min in WKY vs. 112 +/- 2.6 in the SHR, P less than 0.001) and binding (154 +/- 3.0 nmol/mg per min in WKY vs. 101 +/- 1.8 in the SHR, P less than 0.01) were decreased in the SHR. Ca2+-ATPase activity, however, was significantly higher in the SHR (118 +/- 3.1 nmol of P per mg of protein per min vs. 86 +/- 1.1 in the WKY, P less than 0.001), suggesting "uncoupling" of the ATPase to calcium transport. Cyclic AMP-dependent phosphorylation of SR was significantly decreased in SHR (0.71 +/- 0.05 vs 0.32 +/- 0.07 nmol of P/mg of protein per 10 min, P less than 0.001) and there was an excellent correlation between cyclic AMP-induced phosphorylation of SR and Ca2+ uptake (r = 0.81). Differences in both cyclic AMP-dependent phosphorylation and Ca2+ uptake between the two groups were evident at 10 weeks and increased progressively to 22 weeks of age. Differences in endogenous cyclic AMP-dependent protein kinase activity may partly explain the decreased Ca2+ transport in SHR.

Adenosine Triphosphatases↗
PubMed1976

Effects of indomethacin on renomedullary interstitial cells.

The effects of indomethacin, an inhibitor of prostaglandin synthesis, on rat renomedullary interstitial cells were studied. Indomethacin, 5 mg. per kg. intravenously in divided doses over 48 hours, resulted in reduced granularity of interstitial cells (5.56+/-1.37 versus 9.85+/-1.07 granules per cell, (p is less than 0.001) and, at the same time, inhibited the incorporation of 14C-arachidonate into renomedullary phospholipids (715 + 11 versus 1299 + 42 c.pm.per mug. of lipid orthophosphate; p is less than 0.001) 14C-arachidonate incorporation into cortical phospholipids was not affected by indomethacin. There was a close correlation between individual granule counts and 14C-arachidonate incorporation into medullary phospholipids for both control (r=0.85) and indomethacin-treated animals (r=0.9). Radioactivity in the cytosol fraction was depressed by indomethacin reflecting inhibition of prostaglandin synthesis; cytosol radioactivity correlated closely with individual granule count (r=0.81) in the indomethacin-treated but not in the control rats. Indomethacin given as a single dose 4 hours prior to sacrifice resulted in a significant depression of 14C-arachidonate incorporation but did not affect granularity of interstitial cells. The results suggest that granularity of renomedullary interstitial cells reflects the activity of prostaglandin synthesis and the rate of prostaglandin precursor delivery from microsomal phospholipids.

Animals↗
PubMed1976

Renomedullary interstitial cells in the spontaneously hypertensive rat.

Renomedullary interstitial cells (RIC) are known to synthesize and release prostaglandins which may play a significant role in the development or severity of hypertension. The medulla of the spontaneously hypertensive rat contains RIC which are morphologically very similar to those previously described in the normotensive rat. The granularity of the RIC, however, was increased in the spontaneously hypertensive rat compared to normotensive Wistars (9.6 +/- 2.34 versus 5.3 +/- 2.05 granules per cell, respectively, p less than 0.001) or treated spontaneously hypertensive rats (7.2 +/- 1.65 granules per cell, p less than 0.001). Granule counts also increased in the presence of mild and moderate degrees of renal arteriolar sclerosis, but decreased in long standing hypertension with more severe and extensive lesions involving both arteries and arterioles. These results are consistent with the hypothesis that the RIC respond to an elevation of blood pressure in the spontaneously hypertensive rats by increased release of antihypertensive substances. In addition, the decrease in granularity of the RIC in the presence of extensive renal arteriolar and arterial damage suggests reduced ability to compensate for the elevated blood pressure and thus may contribute to the acceleration of hypertension.

Aging↗
PubMed1975

Comparison of the handling of norepinephrine in the myocardium of adult and old rats.

The handling of norepinephrine was compared in the myocardium of adult and old rats. Endogenous norepinephrine levels were significantly lower in the hearts of old animals. Following intravenous injection of 3H-norepinephrine [3H-NE] the initial uptake was slightly higher in the old animals; subsequently, however, there was a more pronounced and prolonged fall in 3H-NE specific activity in the myocardium of the old rats. The increased turnover rate was associated with normal catecholamine synthesis. Studies of the subcellular distribution of 3H-NE showed an inability of the myocardium from ageing rats to retain norepinephrine in the storage granules with subsequent loss of the soluble fraction.

Aging↗