Disease relevance of KLKB1

• Pathogenesis of periodontitis: a major arginine-specific cysteine proteinase from Porphyromonas gingivalis induces vascular permeability enhancement through activation of the kallikrein/kinin pathway [1].
• The effect of hemorrhagic hypotension on urinary kallikrein excretion, renin activity, and renal cortical blood flow in the pig [2].
• The known inhibitory effect of Trasylol on kallikrein prompted an investigation into the role of kinins in inducing local edema formation [3].
• 4. We identified an expressed sequence tag from an endometrial carcinoma cDNA library with 50% identity to the three known KLK genes [4].
• The antihypertensive effect of oral administration of pig pancreatic kallikrein was investigated in a double blind study of 20 patients with essential hypertension [5].

High impact information on KLKB1

• Pig pancreatic kallikrein liberates kallidin from kininogen, whereas trypsin releases bradykinin [6].
• Ability of kallikrein to generate angiotensin II-like pressor substance and a proposed 'kinin-tensin enzyme system' [6].
• The kininase II/angiotensin-converting enzyme inhibitor enalaprilat and the addition of kininogen or kallikrein enhanced norepinephrine exocytosis by approximately equal to 6% to 40% (EC50, 20 nmol/L) and approximately equal to 25% to 60%, respectively [7].
• Therefore, it seems that urinary kallikrein is activated mainly during the period of autoregulation, whereas renin activity is, in the main, increased below the autoregulatory range of pressure [2].
• Consistent with the finding that a major part of the ASP-induced VL was reduced by a potent kallikrein inhibitor, soybean trypsin inhibitor that does not affect ASP enzymatic activity, ASP activated prekallikrein but not factor XII to generate kallikrein in a dose- and incubation time-dependent manner [8].

Chemical compound and disease context of KLKB1

• Because bradykinin constitutes a possible candidate for mediation of topical 8-methoxypsoralen-UVA-(PUVA)-induced erythema, aprotinin (Trasylol), inhibitor of kallikrein and interrupter of the cascade leading to kinin production was assessed in guinea pigs [9].
• On the first and second postoperative days, mild biochemical signs of pancreatitis were seen in the plasma, including a decrease in kininogen and C3 concentration as well as in plasma kallikrein inhibitory activity and the appearance of trypsin-protease inhibitor complexes [10].
• As long as RCBF was maintained, urinary kallikrein excretion rate was elevated during the progressive hypotension in both saline and saralasin-treated animals [11].
• In the case of T beta-kallikrein, N-termini of the light and the heavy chains were isoleucine and alanine, respectively, and the light chain retained the "kallikrein autolysis loop" region in its C-terminal end [12].
• The cutaneous reactions to kallikrein, prostaglandin and thurfyl nicotinate in chronic urticaria and the effect of polyphloretin phosphate [13].

Biological context of KLKB1

• To determine the identity of porcine follipsin, a plasma kallikrein cDNA clone was isolated from a porcine liver cDNA library [14].
• The ordered kallikrein loop projects proline toward the active site to restrict smaller residues or proline at the P2 position of substrates [15].
• Immunological analyses and substrate specificity studies, together with other existing evidence, indicated that follipsin is distinct from kallikrein and factor XIa, thus being a novel type of serine proteinase [16].
• The permeability activity was short-lasting, and was completely blocked by a kallikrein inhibitor purified from guinea pig plasma, suggesting the presence of a down-regulation system for the permeability activity in vivo [17].
• These data suggest that the human kallikrein gene family locus on chromosome 19 is larger than previously thought and also indicate a greater sequence divergence within this family compared with the highly conserved rodent kallikrein genes [4].

Anatomical context of KLKB1

• These results indicate that porcine follipsin is plasma kallikrein, and that the enzyme may be involved in the production of bradykinin within ovarian follicles [14].
• A sequence coding for a peptide with 57% homology to the only complete kallikrein sequence reported to date (from pig pancreas) was identified by a computer search program [18].
• Aprotinin, the serine protease inhibitor that also inhibits glandular (urinary) kallikrein, or vehicle was infused into the aorta above the renal arteries of anesthetized pigs [19].
• Purification and properties of guinea-pig submandibular-gland kallikrein [20].
• In addition tissue kallikrein was found by immunohistochemistry to be present in the extracellular matrix of the intima of porcine aortic vessel wall [21].

Associations of KLKB1 with chemical compounds

• Identification of porcine follipsin as plasma kallikrein, and its possible involvement in the production of bradykinin within the follicles of porcine ovaries [14].
• The protein has been shown to be a potent active site-directed inhibitor of thrombin and the contact enzymes Factor XIIf, Factor XIa, and kallikrein [22].
• The C2-deficient guinea pigs respond normally to injections of bradykinin and kallikrein, suggesting that these animals can respond to kinins and have a normal kininogen pathway [23].
• Substrate specificity studies using synthetic and peptide substrates indicated that the enzyme preferentially hydrolyzes Arg-X bonds and, to a much lesser extent, Lys-X bonds, and is apparently distinct from thrombin, kallikrein, plasmin, and other trypsin-like proteinases so far reported including tryptase [24].
• Chronic COI administration in Wistar rats suggests that ASA, meclofenamate, and indomethacin affect both the plasma kallikrein-kinin system and kallikrein excretion [25].

Other interactions of KLKB1

• ES-8891 did not inhibit cathepsin D, pepsin, trypsin, chymotrypsin, angiotensin converting enzyme, and urinary kallikrein at a concentration of 10(-5) M [26].
• The other factors, prekallikrein, kallikrein inhibitor, alpha 2-antiplasmin, prothrombin, and antithrombin-III were all released by the liver and underwent partial hepatic inactivation [27].
• It did not inhibit cathepsin D, carboxypeptidase A, pancreatic kallikrein or trypsin [28].
• I alpha IH4 is unique compared with the three other inter-alpha-trypsin inhibitor heavy chains as it does not contain a binding site for bikunin that has serine protease inhibitory activity and is sensitive to cleavage by kallikrein [29].
• In surviving pigs (n = 14), biochemical signs of protease activation evolved in plasma, including formation of trypsin-protease inhibitor complexes, a decline in C3 and kininogen levels, and a decline in functionally active alpha 2-macroglobulin, functionally active antithrombin III, and plasma kallikrein inhibitory activity [30].

Analytical, diagnostic and therapeutic context of KLKB1

• Refined 2 A X-ray crystal structure of porcine pancreatic kallikrein A, a specific trypsin-like serine proteinase. Crystallization, structure determination, crystallographic refinement, structure and its comparison with bovine trypsin [31].
• Hepatic synthesis of kallikrein and plasmin remained depressed after reperfusion, and that of plasminogen fell to zero [27].
• A role for kallikrein/bradykinin in hepatic blood flow regulation is proposed and implications of these observations for liver transplantation are discussed [27].
• Using an enzyme-linked immunosorbent assay with sheep serum raised against rat urinary kallikrein, the glandular kallikrein concentration of FPI was estimated to be 4.56 +/- 0.857 micrograms/mg protein [32].
• In contrast, these bis-cationic ligands bound pancreatic kallikrein in solution and following immobilization [33].

References