Disease relevance of Kng1

• Genetic kininogen deficiency contributes to aortic aneurysm formation but not to atherosclerosis [1].
• Here we present data demonstrating that genetic kininogen deficiency promotes the formation of aneurysms in the abdominal aorta but not the development of atherosclerosis upon 12-wk treatment with an atherogenic diet [1].
• Finally, in response to atherogenic diet, kininogen-deficient animals developed an increase in HDL/total cholesterol index, pronounced fatty liver and heart degeneration, and lipid depositions in aortic media without atherosclerotic plaque formation [1].
• Kallikrein-kininogen system activation and bradykinin (B2) receptors in indomethacin induced enterocolitis in genetically susceptible Lewis rats [2].
• Differential effects of ureteral obstruction on rat kininogen gene family [3].

High impact information on Kng1

• Rat aortic smooth muscle cells in culture express kallikrein, kininogen, and bradykininase activity [4].
• Other serine proteinases, including trypsin, either did not induce contraction in the absence of added kininogen or did so minimally [5].
• Although small amounts of kininogen-like substrate were found in uterine tissue, detectable kinin levels (greater than 4 pg) could not be found in bathing media during maximal kallikrein-induced contractions or after uterine tissue was incubated with high concentrations of the enzyme in the presence of SQ 20881, a kininase II inhibitor [5].
• Kallikrein caused an immediate series of rhythmic contractions which could be increased gradually with subsequent addition of kininogen substrate [5].
• Proteolysis of plasma high molecular weight kininogen (HK) yielding bradykinin and cleaved HK (HKa) was faster in Lewis than in Fischer or Buffalo rat plasma [6].

Chemical compound and disease context of Kng1

• Pretreatment with TCV309 caused a near complete inhibition of the LPS-induced hypotension in kininogen-deficient and normal B/N rats [7].
• Although it is well known that cysteine proteases are strongly inhibited by kininogen, cathepsin L could represent an alternative pathway for kinin production in pathological processes [8].
• Effect of dexamethasone on kininogen production by a rat hepatoma cell line [9].
• The initial phase, occurring within 3 h, of paw edema induced by cardiotoxin was suppressed by trasylol, [Thi5,8,D-Phe7]bradykinin, or by cellulose sulfate pretreatment which greatly reduced plasma kininogen levels [10].
• Acute pulmonary edema and plasma kininogen consumption in the adrenaline-treated rat: inhibition by acetylsalicylic acid and resistance to salicylate and indomethacin [11].

Biological context of Kng1

• Comparison of the nucleotide sequence in the 5' proximal flanking region (1 kilobase) of a strongly inducible alpha 1-MAP gene with that in the non-inducible rat kininogen gene showed an overall homology of 90%, with a small number of randomly distributed base changes [12].
• Various features of the DNA related to gene expression such as initiation and termination sites of transcription, receptor binding sites, a Z-DNA section, and exon/intron splicing sites were identified. mRNAs expressed by alpha 1-MAP and kininogen genes in liver were studied by RNA blot hybridization using specific oligonucleotide probes [12].
• Differing utilization of homologous transcription initiation sites of rat K and T kininogen genes under inflammation condition [13].
• A gene encoding the acute-phase reactant, T-kininogen, has been isolated from a rat genomic library [14].
• BN/Ka rats are characterized by a single point mutation in the kininogen gene leading to deficiency in high- and low-molecular-weight kininogen [1].

Anatomical context of Kng1

• Incubation of normal mouse mast cells with affinity-purified GEF or bradykinin, a product of cleavage of kininogen by kallikrein, resulted in the release of histamine and arachidonate from the cells [15].
• In this study, we constructed a series of chimeric kininogen genes by exchanging equivalent restriction fragments of the K and T genes and examined the sequences and the mechanisms governing the different expression patterns of the kininogen genes by introducing the chimeric genes into heterologous COS cells [16].
• Kininogen and kinin in experimental spinal cord injury [17].
• Total kininogen levels in the hypothalamus were undetectable during pregnancy; however, anterior pituitary kininogen levels increased markedly from days 15-22 [18].
• The incubation of four rat uterine horns with kallikrein in the presence of a uterine horn previously depleted of kininogen elicited contractions of the depleted uterus [19].

Associations of Kng1 with chemical compounds

• LMW kininogen is a precursor of bradykinin. alpha 1-MAP does contain a bradykinin sequence; the flanking amino acids are different, however [20].
• In the intron downstream of the exon coding for Ile-Ser-bradykinin, the two alpha 1-MAP genes contained sequence sections similar to the section in the human kininogen gene which codes for the carboxyl-terminal chain of high molecular weight kininogen [12].
• In order to more fully understand this role, we have examined the interleukin-6 induction of T kininogen, a cysteine protease inhibitor and a major acute phase reactant in the rat [21].
• They show a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the presence and absence of 2-mercaptoethanol, and the molecular weights are 68,000 for low Mr kininogen A and 73,000 for low Mr kininogen B [22].
• The COOH-terminal portion of low Mr kininogen A was isolated after cyanogen bromide treatment, and the amino acid sequence of the COOH-terminal 55 residues including the T-kinin (Ile-Ser-bradykinin) was determined [22].

Other interactions of Kng1

• The two T kininogen (T) mRNAs considerably increase under acute inflammation conditions, although no such increase occurs in the high molecular weight and low molecular weight K kininogen (K) mRNAs encoded by the same gene [13].
• Plasma prekallikrein (amidolytic), high molecular weight kininogen (HK, coagulant) and cleavage of HK (western blot) were assayed to detect K-K activation [2].
• Proteinase A with Mr of 28,200 rapidly cleaved high-molecular-weight (HMW) kininogen into a protein of 67 kDa, which retained thiol-proteinase inhibitory activity, but had lost the correcting activity of HMW kininogen on the prolonged clotting time of Fitzgerald trait plasma [23].
• This oestrogen-induced increase of blood flow was reduced significantly by pretreatment with mepyramine (a histamine H1-receptor antagonist), cellulose sulphate (a kininogen-depleting agent) and aprotinin (a kininogenase inhibitor) [24].
• The peptide was tested with rat plasma and urine kallikrein, which resulting in an inhibition with similar affinity to both enzymes, showing an IC50 of 14.3 microM after 13 and 8 min, respectively, using kininogen as substrate on the isolated guinea-pig ileum bioassay [25].

Analytical, diagnostic and therapeutic context of Kng1

• The present investigation using molecular cloning and sequence analysis concerns the examination of the molecular basis for different expression patterns of two types of the rat kininogen genes [26].
• Specific activity, as determined by enzyme-linked immunosorbent assay (ELISA), was 0.972 mg kininogen equivalent per mg protein [27].
• GKLE, kininogen, and bradykininase activity were all present in VSM cells grown in defined media that contain no serum, thus eliminating any contamination or artefacts from fetal calf serum in standard culture media [4].
• The purified enzyme has N alpha-tosyl-L-arginine methyl esterase activity with a pH optimum at 9.0, kinin-releasing activity from a purified low molecular weight kininogen, and a parallelism with standard curves of rat urinary kallikrein in a direct radioimmunoassay [28].
• It hydrolyzed benzyloxylcarbonyl-Gly-Gly-Arg-amino-4-trifluoromethyl coumarin, and a Km of 53 microM and a Vmax of 63 mumol/min/mg of enzyme were obtained at pH 8.0 and 37 degrees C. The enzyme cleaved kininogen substrates to produce kinin which was measured by bioassay or radioimmunoassay [29].

References