Disease relevance of Cpn1

• The possible correlation between the severity of CPN and the incidence of pheochromocytoma may influence interpretation of carcinogenic effects observed at this site [1].
• Serum CPN concentrations were not significantly increased in rats with primary sarcomas (mean = 0.38 g per liter) (S.D. +/- 0.05), versus 0.35 g per liter (S.D. +/- 0.04) in controls [2].
• Many chemicals are known to exacerbate the severity of CPN to an advanced stage, and this interaction between chemical and CPN can result in a small increase in the incidence of renal adenomas in 2-year carcinogenicity bioassays [3].

High impact information on Cpn1

• Since CPN does not interact significantly with hepatocytes, its presence in bile suggests transcytosis via the biliary epithelium [4].
• Using an antibody to CPN which reacts also with AsCPN, we found about 70% of the bile radioactivity to be immunoprecipitable following injections of either glycoprotein, indicating that a fraction of these copper proteins had entered the bile essentially unmodified [4].
• In addition to Lys-Lys-BK (B1087), which is partially resistant to ACE, [Hyp3,Phe8-r-Arg9]BK (B7642) was completely resistant to ACE, CPN, and the unidentified plasma activity (1.9 +/- 0.3 nmol/min/ml), and D-Arg0[Hyp3,Phe8-r-Arg9]BK (B7644) was resistant to all plasma hydrolysis, including APP (less than 0.2 nmol/min/ml) [5].
• In addition to angiotensin I converting enzyme (ACE; EC 3.4.15.1) and carboxypeptidase N (CPN; EC 3.4.17.3), other peptidases contribute to bradykinin (BK) degradation in plasma [6].
• Useful modifications compatible with agonistic activity included D-Arg0 (protects against APP), D-N-methyl-Phe7 and dehydro-Phe5 (protect against ACE), and erythro-phenylserine or erythro-amino-phenyl-butyric acid at position 8 (protect against ACE and CPN) [7].

Chemical compound and disease context of Cpn1

• Ceruloplasmin (CPN) concentrations were measured by p-phenylenediamine oxidase assay in serums from (a) 30 control Fischer rats; (b) 5 rats with primary sarcomas induced by i.m. injection of nickel subsulfide (alpha Ni3S2), and (c) 12 rats at intervals up to six weeks after s.c. transplantation of four alpha Ni3S2-induced sarcomas [2].

Biological context of Cpn1

• CPN (chronic progressive nephropathy) is a spontaneous age-related disease that occurs in high incidence in the strains of rat commonly used in preclinical toxicology studies, exhibiting a male predisposition [3].

Associations of Cpn1 with chemical compounds

• Carboxypeptidase R (EC 3.4.17.20) (CPR) and carboxypeptidase N (EC 3.4.17.3) (CPN) cleave carboxy-terminal arginine or lysine residues from biologically active peptides such as kinins or anaphylatoxins in the circulation thereby regulating their activities [8].
• With both doses of rhIL-1 beta, iron, albumin, CPN, and lysine were significantly decreased whereas alpha 2-globulin, urea, and creatinine were significantly increased 12 hr after administration [9].
• Treatment with oxyphenylbutazone and hydrocortisone failed to inhibit the raised serum CPN levels [10].
• Serum ceruloplasmin (CPN) levels under different types of acute and chronic experimentally-induced inflammatory conditions in rats and the effect of anti-inflammatory drugs viz. oxyphenylbutazone and hydrocortisone on serum CPN levels were investigated [10].

Analytical, diagnostic and therapeutic context of Cpn1

• To elucidate the complex role of CPN and CPR in vivo, studies in animal models will be essential [11].
• Maximum concentrations of serum CPN occurred at 31 to 34 days after tumor transplantation, (mean = 0.56 +/- 0.05 g per liter), equivalent to 1.6 +/- 0.2 times the initial CPN concentrations in serums obtained prior to treatment (P less than 0.001) [2].
• The precise etiology of CPN and the mechanism(s) underlying its pathogenesis remain unknown, but the long-standing assumption that glomerular dysfunction is the primary basis is challenged in the light of contemporary developments in understanding filtration and postglomerular cellular processing of albumin [3].

References