Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to determine whether the kallikrein-kinin system exerts a protective action in hypertension induced by chronic inhibition of nitric oxide synthase. N omega-nitro-L-arginine methyl ester (L-NAME, 40 mg/100 ml water) was given orally to Sprague-Dawley rats, while controls received regular tap water. Hepatic kininogen mRNA levels in the L-NAME-treated group were 2.9- and 2.5-fold higher at 3 and 4 wk, respectively, compared with control rats, whereas kallikrein-binding protein (KBP) mRNA levels were 82% and 45% of the values found in control rats at 3 and 4 wk, respectively. There was no significant change in hepatic alpha 1-antitrypsin mRNA levels under the same conditions. At 3 and 4 wk post L-NAME treatment, renal kallikrein mRNA levels were 2.5- and 3.4-fold higher than in controls, whereas renal beta-actin mRNA levels were similar between groups. Changes in the transcript levels of renal kallikrein, kininogen, and KBP were consistent with their protein levels. Immunoreactive total kininogen and low-Mr kininogen levels in sera and tissue kallikrein levels in kidney were significantly higher in the L-NAME-treated group, whereas KBP levels in the circulation were lower compared with controls. Systolic blood pressure was increased by 58 +/- 4 mmHg after 4 wk of L-NAME treatment. This effect was enhanced in rats given L-NAME in combination with HOE-140, a bradykinin B2-receptor antagonist, at the dose of 100 micrograms/day ip (79 +/- 5 vs. 58 +/- 4 mmHg, P < 0.05). This difference was confirmed by direct measurement of mean blood pressure (MBP). An intra-arterial bolus injection of 200 ng bradykinin significantly decreased MBP of L-NAME-treated rats, and this effect was blunted in the group treated with the bradykinin antagonist (-29 +/- 3 vs. -9 +/- 2 mmHg, P < 0.01). These results suggest that enhanced kallikrein and kininogen synthesis may have a protective role against the cardiovascular effects induced by chronic inhibition of nitric oxide synthesis.
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PMID:Differential regulation of kallikrein, kininogen, and kallikrein-binding protein in arterial hypertensive rats. 876 Feb 46

Significant levels of adenovirus (Ad)-mediated gene transfer occur only in immature muscle or in regenerating muscle, indicating that a developmentally regulated event plays a major role in limiting transgene expression in mature skeletal muscle. We have previously shown that in developing mouse muscle, expression of the primary Ad receptor CAR is severely downregulated during muscle maturation. To evaluate how global expression of CAR throughout muscle affects Ad vector (AdV)-mediated gene transfer into mature skeletal muscle, we produced transgenic mice that express the CAR cDNA under the control of the muscle-specific creatine kinase promoter. Five-month-old transgenic mice were compared to their nontransgenic littermates for their susceptibility to AdV transduction. In CAR transgenics that had been injected in the tibialis anterior muscle with AdVCMVlacZ, increased gene transfer was demonstrated by the increase in the number of transduced muscle fibers (433 +/- 121 in transgenic mice versus 8 +/- 4 in nontransgenic littermates) as well as the 25-fold increase in overall beta-galactosidase activity. Even when the reporter gene was driven by a more efficient promoter (the cytomegalovirus enhancer-chicken beta-actin gene promoter), differential transducibility was still evident (893 +/- 149 versus 153 +/- 30 fibers; P < 0.001). Furthermore, a fivefold decrease in the titer of injected AdV still resulted in significant transduction of muscle (253 +/- 130 versus 14 +/- 4 fibers). The dramatic enhancement in AdV-mediated gene transfer to mature skeletal muscle that is observed in the CAR transgenics indicates that prior modulation of the level of CAR expression can overcome the poor AdV transducibility of mature skeletal muscle and significant transduction can be obtained at low titers of AdV.
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PMID:Muscle-specific overexpression of the adenovirus primary receptor CAR overcomes low efficiency of gene transfer to mature skeletal muscle. 1128 77

The effect of aerosolized adrenomedullin on interleukin-1 beta and transforming growth factor (TGF)-beta1 mRNA and protein expression was studied in surfactant depleted piglets, receiving aerosolized adrenomedullin (adrenomedullin, n=6), aerosolized adrenomedullin plus i.v. N(G)-nitro-L-arginine-methylester (adrenomedullin+L-NAME, n=5), or aerosolized saline solution (control, n=6). After 8 h of aerosol interval therapy, mRNA expression of interleukin-1 beta and TGF-beta1 in lung tissue was quantified normalized to beta-actin and hypoxanthine-guanine-phosphoribosyl-transferase by real-time polymerase chain reaction (PCR). Interleukin-1 beta and TGF-beta1 protein concentration in lung tissue was quantified by enzyme-linked immunosorbent assay (ELISA). In the adrenomedullin group, interleukin-1 beta and TGF-beta1 mRNA expression was lower than in controls. Reduction for interleukin-1 beta/beta-actin was 56% (p<0.001), for interleukin-1 beta/hypoxanthine-guanine-phosphoribosyl-transferase 60% (p<0.001), for TGF-beta1/beta-actin 65.5% (p<0.001), and for TGF-beta1/hypoxanthine-guanine-phosphoribosyl-transferase 56.2% (p<0.001). Mean interleukin-1 beta protein expression was different between the groups, p<0.05 (adrenomedullin 601+/-61, Control 836+/-88 pg/mg protein). L-NAME did not antagonize adrenomedullin effect on TGF-beta1 mRNA. In conclusion, aerosolized adrenomedullin reduced pulmonary inflammatory and pro-fibrotic response.
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PMID:Aerosolized adrenomedullin suppresses pulmonary transforming growth factor-beta1 and interleukin-1 beta gene expression in vivo. 1246 Jun 45