Disease relevance of KNG

• Hypertension induced by a nonpressor dose of angiotensin II in kininogen-deficient rats [1].
• Intravenous administration of the enzyme bromelain, which reduces plasma kininogen levels, inhibited the footpad edema induced with carrageenin or with a mixture of carrageenin and forskolin [2].

High impact information on KNG

• This suggests that the mRNAs are transcribed from the same gene to generate two LMW kininogen precursors differing only in the internally homologous sequences [3].
• By using a mixture of synthetic oligodeoxyribonucleotides as a probe, cloned cDNA sequences specific for low molecular weight (LMW) kininogen have been isolated from a cDNA library of bovine liver mRNA sequences [3].
• Kinin formation from the high Mr kininogen is catalyzed by porcine pancreatic kallikrein or trypsin [4].
• Bovine high molecular weight kininogen. The amino acid sequence, positions of carbohydrate chains and disulfide bridges in the heavy chain portion [5].
• A high histidine content in the light chain of rat high Mr kininogen indicated the presence of a histidine-rich region in this protein as in bovine high Mr kininogen, although this region was not cleaved by rat plasma kallikrein [6].

Biological context of KNG

• The systolic blood pressure of 7-week-old kininogen-deficient rats (132 +/- 2 mmHg, n = 7) was not different from that of normal rats [1].
• Mapping the binding site of tissue kallikrein: preparation and testing of all possible substrate analog inhibitors homologous with the sequence of kininogen between Ser386 and Gln392 [7].
• 3. Changes in both kinin and kininogen levels on day 3 coincided with the detection of low levels of parasites, and with a fall in packed cell volume [8].
• The highest k(cat)/Km value in the hydrolysis of Abz-[Gln370-Gln381]-bkng-EDDnp by pk1 demonstrates an important interaction of subsites S5-S4 with Gln and Thr residues in the bovine kininogen segment [9].
• The effects of high-Mr kininogen and kaolin surface on the kinetics of these activation reactions were studied [10].

Anatomical context of KNG

• Subcutaneous infusion of bovine low-molecular-weight kininogen with an osmotic pump in Ang II-treated deficient rats induced significant reductions in blood pressure, heart rate, and erythrocyte sodium levels [1].
• In this study, cysteine-proteinase-inhibiting properties of rat T kininogen and of its proteolytic fragments issuing from trypsin and submaxillary gland endopeptidase k hydrolysis, have been investigated using rat lysosomal cathepsins B, H and L, papain and bovine calpains I and II [11].
• The fragments of bovine high molecular weight kininogen promote osteoblast proliferation in vitro [12].
• The proteins each entered fibroblasts by adsorptive pinocytosis and were then degraded within the lysosomes by enzymes susceptible to leupeptin, the thiol-proteinase inhibitor [13].

Associations of KNG with chemical compounds

• The corresponding amino acid sequences show that the LMW kininogen precursors of the two types, composed of 436 and 434 amino acid residues, both contain two internally homologous sequences in the amino-terminal portion between a signal peptide and a bradykinin moiety [3].
• Studies on the primary structure of bovine high-molecular-weight kininogen. Amino acid sequence of a fragment ("histidine-rich peptide") released by plasma kallikrein [14].
• Primary structure of bovine plasma high-molecular-weight kininogen. The amino acid sequence of a glycopeptide portion (fragment 1) following the C-terminus ot the bradykinin moiety [15].
• These results suggest that the lack of kinin generation observed in the kininogen-deficient rats may cause the hypertensive response during the administration of a nonpressor dose of Ang II mainly through sodium retention probably caused by aldosterone release [1].
• Freeze-thaw solubilization was not blocked by the thiol proteinase inhibitor antipain and did not lead to the activation of the enzyme [16].

Physical interactions of KNG

• A systematic approach to evaluate the contribution of individual residues occurring within the sequence Ser386-Pro-Phe-Arg-Ser-Val-Gln392 from bovine kininogen towards binding to tissue kallikrein is developed [17].

Other interactions of KNG

• To this end, all possible substrate analogues occurring within the sequence Ser386-Pro-Phe-Arg-Ser-Val-Gln392 from bovine kininogen were synthesized and tested as inhibitors of tissue kallikrein (EC 3.4.21.35, beta-PPK) [7].
• Functional sites of bovine high molecular weight kininogen as a cofactor in kaolin-mediated activation of factor XII (Hageman factor) [18].
• Highly significant differences were observed in changes to plasma fibrinogen, serum fibrinogen-like proteins, packed cell volume, partial thromboplastin time, prothrombin time, blood kinins, and plasma kininogen levels in the control animals but non-significant changes in these parameters occurred in the group receiving iradiated blood [19].

Analytical, diagnostic and therapeutic context of KNG

• Fast atom bombardment/mass spectrometry analysis further confirmed the occurrence of bradykinin in a pancreatic kallikrein digest of a partially purified bovine milk kininogen preparation [4].
• Kinin formed by tonin from purified LMW kininogen was identified with bradykinin in high performance liquid chromatography and radioimmunoassay [20].
• The densitometric determination of the bands separated on SDS-PAGE and amino acid analysis of the samples extracted from the electrophoresis gel revealed that the complex between kininogen and papain is formed in a molar ratio of one to one [21].
• These results suggest that the enzymatically-digested fragments of bovine HMW kininogen are able to be a naturally occurred active protein that promotes the bone formation by oral administration [12].
• However, this accelerating effect of HMW kininogen on the amylose sulfate- and sulfatide-mediated activations (reaction 1) was diminished after treatment with fluorescein iso-thiocyanate, whereas the effect on the kaolin-mediated activation was not influenced by fluorescein-labeling [22].

References