Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutral endopeptidase (NEP, 24.11) is an ectoenzyme involved in the degradation of peptide hormones such as endothelin (ET), atrial natriuretic factor and enkephalins. The current study was designed to assess the involvement of NEP in ischemia-induced acute renal failure (ARF). In unilaterally nephrectomized Sprague-Dawley rats, the left renal artery was occluded for 30 min under pentobarbital anesthesia (40 mg/kg, i.p.) at 37 degree C. In addition to plasma creatinine levels, NEP activity was determined in renal cortical membranes at 0, 2, 5, and 24 h following reperfusion. Plasma creatinine levels significantly increased at 2, 5 and 24 h. There was a significant decrease in NEP activity as early as 2 h following reperfusion that was maintained up to 24 h (57.9 +/- 4%) with a concomitant loss of enzyme protein shown by Western analysis. Northern analysis of kidney cortical RNA, probed with an NEP cDNA, showed a 45% decrease in NEP mRNA level by the end of the ischemic period and decreased further during reperfusion. Thus, decrease in NEP mRNA levels preceded the changes in protein level, enzyme activity and plasma creatinine levels. These data, along with the reported increase in the tissue level of ET in kidney cortex, and the beneficial effect of ET antibody as well as ET receptor antagonist in ARF, suggest that down regulation of NEP, one of the mechanisms leading to increased tissue level of ET, may be a contributing factor to ARF.
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PMID:Down regulation of kidney neutral endopeptidase mRNA, protein and activity during acute renal failure: possible mechanism for ischemia-induced acute renal failure in rats? 1048 24

Various polypeptide growth factors are generally considered to be involved in the regulation of the nephrogenic process both after acute renal injury and during renal development. Because platelet-derived growth factor B-chain (PDGF-B) has been reported to be expressed in immature tubulus of the developing kidney, PDGF-B could play a role in the process of tubulogenesis. We examined the expression of PDGF-B and PDGF receptors alpha and beta and their localization in kidneys after ischemia/reperfusion injury. The mRNA expressions of PDGF-B, PDGFR-alpha, and PDGFR-beta were enhanced after injury. In the immunohistochemical analysis and/or in situ hybridization, PDGF-B and PDGFR-alpha, beta were expressed after reperfusion in the S3 segment of the proximal tubuli, where they were not expressed normally. The expressions of proliferating cell nuclear antigen and vimentin were concomitantly observed with PDGF-B and PDGFRs in the tubular cells of injured S3 segment at 48 hours after injury. Next, the inhibition of the PDGF-B/PDGFRs axis with either Trapidil or Ki6896, which was found to inhibit the phosphorylation of PDGFR-beta selectively, resulted in a rise of serum creatinine, higher mortality rate, abnormal regenerating process, and suppressed proliferation of tubular epithelial cells. These findings suggest that the PDGF-B/PDGFRs axis is involved in the proliferation of injured tubular cells and plays an important role in the regeneration of tubular cells from acute ischemic injury.
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PMID:Role of PDGF B-chain and PDGF receptors in rat tubular regeneration after acute injury. 1055 Mar 25

Urinary trypin inhibitor concentration (UTI) was measured by Fritz and all method in the groups of women: non-pregnant (I), pregnant (II), in pregnancy complicated by EPH-gestosis (III) and in the prolongated pregnancy (IV). Furthermore, in the urine from the investigated group the index protein/creatinine was established. There was noticed the statistically significant increase in the UTI concentration in II, III, IV groups comparing to the non-pregnant group--I, and the increase in UTI in III and IV group in comparison to group II. The UTI measurement in the pregnant women connected with the index protein/creatinine could be significant for diagnosing of the pathology of pregnancy.
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PMID:[Urinary trypsin inhibitor in pregnant women with normal and pathological course of pregnancy]. 1094 38

MAPK activities, including JNK, p38, and ERK, are markedly enhanced after ischemia in vivo and chemical anoxia in vitro. The relative extent of JNK, p38, or ERK activation has been proposed to determine cell fate after injury. A mouse model was established in which prior exposure to ischemia protected against a second ischemic insult imposed 8 or 15 days later. In contrast to what was observed after 30 min of bilateral ischemia, when a second period of ischemia of 30- or 35-min duration was imposed 8 days later, there was no subsequent increase in plasma creatinine, decrease in glomerular filtration rate, or increase in fractional excretion of sodium. A shorter period of prior ischemia (15 min) was partially protective against subsequent ischemic injury 8 days later. Unilateral ischemia was also protective against a subsequent ischemic insult to the same kidney, revealing that systemic uremia is not necessary for protection. The ischemia-related activation of JNK and p38 and outer medullary vascular congestion were markedly mitigated by prior exposure to ischemia, whereas preconditioning had no effect on post-ischemic activation of ERK1/2. The phosphorylation of MKK7, MKK4, and MKK3/6, upstream activators of JNK and p38, was markedly reduced by ischemic preconditioning, whereas the post-ischemic phosphorylation of MEK1/2, the upstream activator of ERK1/2, was unaffected by preconditioning. Pre- and post-ischemic HSP-25 levels were much higher in the preconditioned kidney. In summary, post-ischemic JNK and p38 (but not ERK1/2) activation was markedly reduced in a model of kidney ischemic preconditioning that was established in the mouse. The reduction in JNK and p38 activation can be accounted for by reduced activation of upstream MAPK kinases. The post-ischemic activation patterns of MAPKs may explain the remarkable protection against ischemic injury observed in this model.
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PMID:Prevention of kidney ischemia/reperfusion-induced functional injury and JNK, p38, and MAPK kinase activation by remote ischemic pretreatment. 1115 Feb 93

Tubular function of 17 pediatric patients with a mild form of acute post-infectious glomerulonephritis was prospectively evaluated by assessment of the urinary activity of proximal and distal tubule enzymes. Neutral-like endopeptidase (NEP-like) and angiotensin-converting enzyme (ACE) were the proximal tubule enzymes assessed, while prolyl-endopeptidase (PE) and serine-endopeptidase H1 and H2 were the distal tubule enzymes analyzed. Urine was collected at diagnosis (T0) and after 2 (T2) and 6 (T6) months of follow-up. NEP-like enzyme activity (nmol/mg creatinine; median+/-quartile range) was increased at diagnosis, and this remained stable during the first 6 months (T0 18.30+/-83.26, T2 17.32+/-49.56, T6 23.38+/-107.18). Urinary activity of the other enzymes was as follows: ACE (mU/ml per mg creatinine) T0 0.08+/-0.16, T2 0.06+/-0.10, T6 0.18+/-0.29; PE (nmol/mg creatinine) T0 6.70+/-84.87, T2 9.55+/-69.00, T6 13.67+/-28.70; serine-endopeptidase H1 (nmol/mg creatinine) T0 7.86+/-26.95, T2 17.17+/-59.37, T6 18.19+/- 79.14; and serine-thiol-endopeptidase H2 (nmol/mg creatinine) T0 3.06+/-21.97, T2 12.06+/-32.42, T6 16.22+/- 44.06. Thirty other healthy children matched for age and gender were considered as a control group. This group was assessed once and the results were: NEP-like activity 6.05+/-10.54, ACE 0.11+/-0.22, PE 7.10+/-13.36, H1 5.00+/-17.30, and H2 6.00+/-20.16. In conclusion, we observed that NEP-like and H1 enzymes exhibited significant increased urinary activity 6 months after the diagnosis. This increase occurred in spite of the disappearance of clinical symptoms, which occurred 2 months after the diagnosis. We believe that the increase in urinary enzymatic activity could be a manifestation of a silent tubular dysfunction following an episode of acute post-infectious glomerulonephritis.
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PMID:Tubular urinary enzymes in acute post-infectious glomerulonephritis. 1151 85

The biochemical and toxicological effects of occupational and dietary exposure of humans to cyanide poisoning from large-scale cassava processing and ingestion of cassava foods were investigated using spectrophotometric and enzymatic methods. Analysis of urinary and serum thiocyanate (cyanide metabolite) from workers in cassava processing industries, who were 'frequent' [those who eat cassava food(s) at least once a day] and 'infrequent' [those who eat cassava food(s) only occasionally] consumers of cassava-based diets, was carried out with the aid of questionnaries. The mean urinary thiocyanate level of the cassava processors (mean+/-S.D.; 153.50+/-25.21 micromo1/l) was 2.2 and 2.6 times higher than that of frequent (70.1+/-21.8 micromo1/l) and infrequent (mean+/-S.D.; 59.30+/-17.0 micromo1/l) cassava consumers, respectively. The mean serum thiocyanate levels rose to 126.73+/-12.4 micromo1/l for the former and 68.4+/-18.3 and 54.7+/-13.2 micromo1/l, respectively, for the latter. An increase in plasma activity by 10% above normal of aspartate aminotransferase (AST) was observed in 40% of the cassava processors, whereas it was within normal range in all consumers. The activities of alanine aminotransferase (ALT) and alkaline phosphatase (ALK.PHOS) were within the normal value in all cases studied. The blood glucose level of 50% of the cassava processors was 100 mg/ml or above while that of the consumers was in the range of 68-85 mg/100 ml. The total protein, serum albumin and creatinine levels were in the range for normal values for the processors and consumers. The health implications of these findings are discussed.
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PMID:Occupational and dietary exposures of humans to cyanide poisoning from large-scale cassava processing and ingestion of cassava foods. 1206 22

The objective was to study toxin-induced effects on physiological parameters in the rabbit and whether these parameters show dose-response and co-variation after administration of a recombinant fusion protein between staphylococcal enterotoxin (SE) and the Fab fragment of an antibody. Rabbits are very sensitive to SE toxins and the cardiovascular and immune effects are similar to those observed in septic shock in man. The test compound, r-C242 Fab-SEA, was administered intravenously to anaesthetised New Zealand white rabbits at doses in the range of 0.00005-50 microg/kg. All rabbits were checked for titres of anti-SEA antibodies before entering the experiment, since they could neutralise the effect of the test compound. Heart rate, blood pressure and body temperature were continuously monitored before and during 6 h after dosing. Immediately before the start of administration and 3 and 6 h during the experiment, blood gases (pO(2) and pCO(2)), pH, haematology, clinical chemistry, cytokine response (TNF-alpha) and trace elements (Mn, Cu, Zn, Se, Ag, Cd, Hg and Pb) were measured. No mortality occurred, but at 50 microg/kg severe adverse clinical signs developed. The decrease in blood pressure was weakly dose-related. Heart rate, ECG, body temperature, pCO(2) and pH were not affected by the treatment. pO(2) tended to increase as a function of time, but not in relation to dose. WBC and PLT decreased dose dependently. TNF-alpha was not affected by the treatment. The major effects on clinical chemistry were a dose-dependent increase in AST and creatinine. Potassium and urea showed dose dependent increases, mainly at higher doses, though these changes were of less value for drug selection purposes. Trace element changes were observed, including an increase in Mn and a decrease of Zn at all doses. The Cu/Zn ratio decreased below normal at low doses, whereas at high doses in which adverse effects developed, it increased above normal. Post mortem examination revealed minimal to moderate dose-related granulocytic infiltrate in the lungs. The present study showed dose-response and co-variation between several changes in cardiovascular, haematology, clinical chemistry and trace element parameters during the initial phase of toxin-induced effects preceding a possible lethal endpoint and associated patho-physiological changes.
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PMID:Effects of a superantigen-antibody recombinant fusion protein (r-C242 Fab-SEA) on toxicological responses in the anaesthetised rabbit. 1250 54

Urine bile acid (UBA) tests reflecting "average" serum bile acid (SBA) concentrations may have greater practical utility than paired SBA samples in cats. This study evaluated whether urine sulfated bile acids (USBAs), urine nousulfated bile acids (UNSBAs), or a combined approach had a clinical utility equivalent to SBAs. Routine serum biochemistry tests, SBA concentrations, and urine samples were collected from 54 cats with hepatobiliary disease, 17 cats with nonhepatic disorders, and 8 healthy cats. UBAs were measured by a quantitative enzymatic colorimetric method, and results were normalized with urine creatinine (UCr) concentrations. Significantly higher values occurred in cats with liver disease than in cats without liver disease for USBA : UCr, UNSBA:UCr, and (USBA and UNSBA) : UCr, P < .05 each. UBA tests with diagnostic performance (sensitivity [SS], specificity [SP], and positive and negative predictive values [PV+ and PV-]) equivalent to SBAs were the UNSBA : UCr and the combined test (SS: 87, 87 versus 85; SP: 88, 88 versus 88; PV+: 96, 96 versus 96; PV-: 68, 65 versus 68; UNSBA : UCr, [USBA, and UNSBA]: UCr versus SBA, respectively). Clinical applications of the UNSBA : UCr or the combined (USBA and UNSBA) : UCr test should be useful as convenient diagnostic tests for identifying cats with liver disease and high SEA concentrations.
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PMID:Urine sulfated and nonsulfated bile acids as a diagnostic test for liver disease in cats. 1452 24

To assess the relation between urinary endogenous sex steroid levels and the risk of postmenopausal breast cancer, a nested case-cohort study was conducted within a large cohort (the DOM cohort) in the Netherlands (n=9,349). Until the end of follow-up (1 January 1996), 397 postmenopausal breast cancer cases were identified and a subcohort of 424 women was then taken from all eligible women. Women using hormones were excluded, leaving 364 breast cancer cases and 382 women in the subcohort for the analyses. Concentrations of oestrone, oestradiol, testosterone, 5alpha-androstane-3alpha, 17beta-diol and creatinine were measured in first morning urine samples, which had been stored since enrolment at -20 degrees C. A Cox proportional Hazards model was used, with Barlow's adjustment for case-cohort sampling, to estimate breast cancer risk in quartiles of each of the, creatinine corrected, hormone levels, the lowest quartile being the reference group. Women with higher levels of all four of the hormones were at increased risk for postmenopausal breast cancer (highest vs lowest quartile: incidence rate ratio for oestrone (IRR(oestrone)=2.5, 95% CI: 1.6-3.8; IRR(oestradiol)=1.5, 95% CI: 1.0-2.3; IRR(testosterone)=1.6, 95% CI: 1.0-2.4; IRR(5alpha-androstane-3alpha, 17beta-diol)=1.7, 95% CI: 1.1-2.7). In conclusion, women with higher excretion levels of both oestrogens and androgens have an increased risk of breast cancer.
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PMID:Urinary endogenous sex hormone levels and the risk of postmenopausal breast cancer. 1277 67

Reperfusion injuries after organ transplantation affect graft function and influence long-term graft survival. As hypothermic storage, which minimizes the extent of unspecific tissue injury after ischemia and reperfusion, is significantly influenced by the composition of preservation solutions, strategies to optimize the different components may lead to longer graft survival. In the present study the effects of the preservation solution B2 on early renal function and histopathological changes were compared to histidine-tryptophan-ketoglutarate solution (HTK, Bretschneider) in a model of isolated blood-perfused porcine kidneys. B2-preserved kidneys displayed a lower renal resistance and significantly better creatinine clearance as compared to HTK. Mean differences were also found for filtration fraction and sodium fraction reabsorption. The functional data were also related to histopathological changes. Together, these data indicate that the recently developed preservation solution B2 offers new principles of preservation and is a useful preservation solution for experimental isolated perfused kidney models. B2 may also be an interesting model for optimizing preservation within other organ perfusion models.
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PMID:Protective effects of B2 preservation solution in comparison to a standard solution (histidine-tryptophan-ketoglutarate/Bretschneider) in a model of isolated autologous hemoperfused porcine kidney. 1498 62


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