Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that normal Wistar rats fed for 3 weeks with an isocaloric sucrose-rich (63%) diet (SRD) develop high levels of plasma free fatty acids and increased triacylglycerol content in the myocardium. We are now reporting that these changes are accompanied by remarkably low levels of the active form of the pyruvate dehydrogenase complex (PDHa; mean +/- SEM, 37.2% +/- 3.7% of the total activity) when compared with levels found in hearts donated by control rats fed the standard chow diet (STD; 71.0% +/- 2.8%; P less than .01). Increased concentrations of both long-chain acyl-CoA (0.21 +/- 0.03 v 0.06 +/- 0.01 mumol.g dry weight-1 found in STD; P less than .01) and acetyl-CoA (0.17 +/- 0.05 v 0.09 +/- 0.01 found in STD; P less than .01), as well as a relative decrease in coenzyme A (CoASH) (0.21 +/- 0.02 v 0.32 +/- 0.05 from STD; P = NS), resulting in an increased acetyl-CoA/CoASH ratio (0.80 +/- 0.13 v 0.29 +/- 0.03 in STD; P less than .01) may have stimulated the PDH kinase, leading in turn to an inactivation of the PDH complex. The above enzymatic and metabolic changes in the in situ heart of SRD-fed rats were still present after perfusing them for 35 minutes with a Krebs-Henseleit buffer containing 11 mmol/L glucose as the only exogenous substrate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biochemical abnormalities in the heart of rats fed a sucrose-rich diet: is the low activity of the pyruvate dehydrogenase complex a result of increased fatty acid oxidation? 198 63

Ovariectomized, adult female rats, with or without estradiol replacement, were kindled by daily amygdala stimulation. Kindling acquisition varied with the intra-amygdala site of stimulation. During stimulation of the medial (AME) or central (ACE) nucleus, the only effect of estradiol replacement (E), compared to non-replaced rats (nE), was to significantly decrease the number of trials with afterdischarge (AD) during early kindling (stage 0). In rats receiving stimulation of the cortical nucleus (ACO) or the baso-lateral group of nuclei (ABL), a similar effect of estradiol was extended through stage 1. In addition, nE rats with ACO or ABL electrodes required significantly more trials with AD and accumulated more than twice the sec of AD during the late stages of kindling, compared to E rats and regressed to lower stage responses between the first stage 4 and last stage 5 responses; regressed responses never occurred in E rats. Estradiol also significantly decreased the prekindling AD threshold of the AME and ACE. These results indicate that estradiol accelerates early stage kindling, likely by proconvulsive properties to increase excitability within immediate amygdala projections. During late kindling stages, estradiol may participate in reinforcing or sustaining the convulsive readiness of kindling circuits established during bilateral recruitment. The site of action for this latter effect of estradiol may reside within circuits accessed by stimulation of the ACO or ABL, and not the AME or ACE.
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PMID:Acquisition of amygdala-kindled seizures in female rats: relationship between the effect of estradiol and intra-amygdaloid electrode location. 368 62

The presence of new hypotensive peptides, possibly not related to ACE inhibition, has been investigated on 66 snake venoms from crotalid, viperid and elapid families. Only the venom of Crotalus atrox showed a substantial amount of a new decapeptide, called POL-236, with the following aminoacid sequence: PYR-LEU-TRP-PRO-ARG-PRO-GLN-ILE-PRO-PRO. Pharmacological assays performed on the synthesized peptide revealed effects on blood pressure, probably derived from vascular and cardiac interferences.
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PMID:A new peptide from Crotalus atrox snake venom. 383 66

To clarify whether various nuclei of the amygdaloid complex play different roles in aggressive behavior including muricide, 4 types of aggression were experimentally induced in rats. These include olfactory bulbectomy (OB rats), midbrain raphe lesions (Raphe rats), administration of delta 9-tetrahydrocannabinol (THC rats) and long-term isolation (Iso rats). Rats which exhibited muricide following these treatments were subjected to bilateral lesions of either the medial (AME), central (ACE) or basolateral (ABL) amygdaloid nuclei. Both muricide and hyperemotionality in the OB rat were markedly inhibited by AME lesions. Those of the Iso and THC rats were moderately inhibited. However, in the Raphe rat, aggressive behavior was not inhibited by AME lesions. Furthermore, ACE or ABL lesions caused no significant changes in all 4 models of aggression. These results suggest that the AME plays a facilitatory role in aggression of OB, Iso and THC rats, but aggression in Raphe rat is independent of amygdaloid activity.
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PMID:Differential effects of medial, central and basolateral amygdaloid lesions on four models of experimentally-induced aggression in rats. 628 23

An epithelial cell line, designated CHK-ACE, was established from the kidney of a spontaneously diabetic Chinese hamster from the highly inbred AC line. CHK-ACE was separated into two sublines, CHK-ACE-100 and CHK-ACE-400, by successive passages in 100 and 400 mg/dl glucose respectively. Extra- and intracellular activities of N-acetyl-beta-D-glucosaminidase and beta-D-galactosidase were measured in these cultures after exposure to varying concentrations of glucose (100, 200, 300 and 400 mg/dl) for one passage and 10% heated fetal calf serum for 6.5 h before enzyme measurements were taken; no apparent dependence on medium-glucose concentration was found. In serum-free medium, the time-dependent release of both N-acetyl-beta-D-glucosaminidase and beta-D-galactosidase was sustained for up to 24 h; no significant difference in their activities was found between CHK-ACE-100 cultures grown in 100 and 400 mg/dl glucose for one passage.
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PMID:Acid glycohydrolase in Chinese hamster with spontaneous diabetes. VII. The lack of short-term glucose-effect in cultured kidney cells. 678 22

An epithelial cell line established from a Chinese hamster kidney, CHK-ACE, was separated into two sublines, CHK-ACE-100 and CHK-ACE-400, by 18 successive passages in medium containing 100 and 400 mg/dl glucose, respectively. Binding of CHK-ACE-100 and CHK-ACE-400 cell to 125I-labeled insulin showed similar pH and time dependency; 125I-labeled insulin, concentration differed in the two sublines, however. Degradation of 125I-labeled insulin, as determined by its ability to bind insulin antibody and cells, was more extensive when preincubated with CHK-ACE-400 cell than with CHK-ACE-100 cells. When CHK-ACE-100 cells were grown in 400 mg/dl glucose for six passages, these cells showed more insulin binding sites than cells grown parallel in 100 mg/dl glucose; whereas CHK-ACE-400 cells grown in 100 mg/dl glucose for six passages showed fewer insulin binding sites than those grown parallel in 400 mg/dl glucose. A slight increase in Kf/Ke ratio was observed in both sublines when grown in 400 mg/dl glucose as compared to 100 mg/dl glucose, indicating attenuated negative cooperativity of the binding sites in cells grown in 400 mg/dl glucose. Tunicamycin, at concentrations from 0.016 to 0.125 micrograms/ml, showed no direct effect on the assay of 125I-labeled insulin binding to CHK-ACE-100 cells; exposure of CHK-ACE-100 cells to tunicamycin, at concentrations from 0.01 to 0.2 micrograms/ml, for 24 h caused a dose-dependent decrease in insulin binding capacity and an increase in Kf/Ke ratio. These data indicate that the number of insulin binding sites in the cultured Chinese hamster kidney epithelial cells increased with high glucose concentrations in the culture medium, whereas tunicamycin, an inhibitor of protein glycosylation, lowered the number of insulin binding sites.
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PMID:Insulin binding in cultured Chinese hamster kidney epithelial cells. The effects of glucose concentration in the medium and tunicamycin. 702 31

Renal crisis occurs in systemic sclerosis patients with rapidly progressive diffuse cutaneous thickening early in their disease course. SRC is characterized by malignant hypertension, hyperreninemia, azotemia, and microangiopathic hemolytic anemia. This complication was almost uniformly fatal but can now be treated successfully in most cases with ACE inhibitors. The result has been improved survival, reduced requirement for dialysis, and even discontinuation of dialysis after 6 to 18 months of treatment. Prompt diagnosis and early aggressive treatment of SRC with ACE inhibitors will result in the most optimal outcome.
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PMID:Renal involvement in systemic sclerosis. 807 63

This study describes the morphology of neurons from the basolateral (ABL), central (ACE), and medial (AM) nuclei of the amygdaloid complex in neonatally undernourished (U) and control (C) Wistar strain rats. The cells were impregnated with the Golgi-Cox technique and studied at the ages of 12, 20, and 40 days postnatally. In the U-pups the neurons of the three nuclei displayed a reduced somatic area compared to that of the C-group on Days 12 and 20. However, at 40 days, this difference diminished due to a reduction in the somatic area of the C-group. The dendritic area also appeared reduced on Days 12 and 20 in the U-group, but on Day 40 it reached control values. The neurons from ABL and ACE suffered a significant decrease in the number of dendritic branches due to undernutrition, but the AM nucleus did not show this change. The data suggest different vulnerability of these amygdaloid nuclei to neonatal undernutrition. The findings also suggest that the abnormal emotional response characteristic of perinatal undernourished rats could have a morphological cause.
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PMID:Neonatal undernutrition and amygdaloid nuclear complex development: an experimental study in the rat. 840 67

Renal crisis occurs in systemic sclerosis patients with rapidly progressive diffuse cutaneous thickening early in their disease. SRC is characterized by malignant hypertension, hyperreninemia, azotemia, microangiopathic hemolytic anemia, and renal failure. This complication, which in the past has been almost uniformly fatal, is now successfully treated in most cases with ACE inhibitors. This therapy has improved survival, reduced requirement for dialysis, and in those on dialysis has often allowed discontinuation of this procedure 6 to 18 months later. Prompt diagnosis and early, aggressive initiation of therapy with ACE inhibitors will result in the most optimal outcome. Chronic nonrenal crisis renal insufficiency is unusual and rarely progresses to significant renal dysfunction.
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PMID:Scleroderma renal crisis. 892

The effect of the blockade of the renin angiotensin system (RAS) on thermoregulatory, cardiovascular and renal function during moderate exercise in a hot [mean (SEM) 34.4 (0.1) degrees C] environment was evaluated. Six men and three women cycled at 60% peak oxygen uptake for 45 min following acute administration of a placebo (PLAC) or enalapril (ENAL), an angiotensin converting enzyme inhibitor (ACE-I). Resting mean arterial pressure (MAP) was reduced by ENAL, but the pressor response to exercise was unaffected [delta MAP = 7.8 (1.4)mmHg for both trials (P > 0.05)]. Peak esophageal temperature [T(es) = 38.7 (1.0) degrees C (PLAC) vs 38.4 (0.2) degrees C (ENAL)] and mean skin temperatures [Tsk = 36.5 (0.1) degrees C (PLAC) vs 36.6 (0.1) degrees C (ENAL)] were similar for both drug treatments during the exercise. Both aldosterone and plasma renin activity (PRA) increased five fold above resting values during exercise; however, only the PRA response [16.7 (3.2) ng angiotensin I (Ang I).ml-1.h-1 (ENAL) vs 7.4 (1.2)ng Ang I.ml-1.h-1 (PLAC)] was significantly altered by ENAL treatment (P < 0.05). Urine flow, sodium excretion and glomerular filtration rates, determined from creatinine clearance, were similarly reduced following exercise for both ENAL and PLAC treatments. These results suggest acute administration (5 mg) of ACE-I does not impair thermoregulatory, cardiovascular or renal responses during moderate exercise in the heat.
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PMID:Influence of angiotensin II blockade during exercise in the heat. 892 29


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