Characterization of human tissue carnosinase

Lenney, James F.; Peppers, Steven C.; Kucera-Orallo, C M; George, Robert P.

doi:10.1042/bj2280653

Cited by 108 publications

(62 citation statements)

References 21 publications

(22 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…l-Carnosine is known to be hydrolyzed by a carnosinedegrading enzyme, carnosinase, which is present in several tissues and serum of humans or animals (Lenney et al, 1985;Kunze et al, 1986;Jackson et al, 1991;Nagai et al, 2003). These findings raise a possibility that enzymatic hydrolysis of exogenous l-carnosine by carnosinase may be involved in l-carnosine actions on ischemic ARF.…”

mentioning

confidence: 76%

“…However, a possibility that l-carnosine improves the I/R-induced renal injury, at least in part, via its antioxidative activity cannot be ruled out, because oxidative stress is definitely involved in the pathogenesis of ischemic ARF (Chatterjee et al, 2000;Takaoka et al, 2002). l-Carnosine is decomposed to ␤-alanine and l-histidine by a carnosine-degrading enzyme, carnosinase, which is present in serum and several tissues (Lenney et al, 1985;Kunze et al, 1986;Jackson et al, 1991;Nagai et al, 2003). In rat brain, two types of carnosine-degrading enzymes are present: one enzyme is carnosinase, which preferentially hydrolyzes carnosine, and the other enzyme hydrolyzes ␤-alanyl-l-arginine considerably faster than carnosine, both of which do not degrade acetyl-l-carnosine (Kunze et al, 1986).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Renoprotective Effects of l-Carnosine on Ischemia/Reperfusion-Induced Renal Injury in Rats

Kurata¹,

Fujii²,

Tsutsui³

et al. 2006

J Pharmacol Exp Ther

View full text Add to dashboard Cite

We examined the renoprotective effects of l-carnosine (␤-alanyl-l-histidine) on ischemia/reperfusion (I/R)-induced acute renal failure (ARF) in rats. Ischemic ARF was induced by occlusion of the left renal artery and vein for 45 min followed by reperfusion, 2 weeks after contralateral nephrectomy. In vehicle (0.9% saline)-treated rats, renal sympathetic nerve activity (RSNA) was significantly augmented during the renal ischemia, and renal function was markedly decreased at 24 h after reperfusion. Intracerebroventricular injection of l-carnosine (1.5 and 5 pmol/rat) to ischemic ARF rats dose-dependently suppressed the augmented RSNA during ischemia and the renal injury at 24 h after reperfusion. N-␣-Acetyl-l-carnosine [N-acetyl-␤-alanyl-l-histidine; 5 pmol/rat intracerebroventricular (i.c.v.)], which is resistant to enzymatic hydrolysis by carnosinase, did not affect the renal injury, and l-histidine (5 pmol/rat i.c.v.), a metabolite cleaved from l-carnosine by carnosinase, ameliorated the I/R-induced renal injury. Furthermore, a selective histamine H 3 receptor antagonist, thioperamide (30 nmol/rat i.c.v.) eliminated the preventing effects by l-carnosine (15 nmol/rat intravenously) on ischemic ARF. In contrast, a selective H 3 receptor agonist, R-␣-methylhistamine (5 pmol/rat i.c.v.), prevented the I/R-induced renal injury as well as l-carnosine (5 pmol/rat) did. These results indicate that l-carnosine prevents the development of I/R-induced renal injury, and the effect is accompanied by suppressing the enhanced RSNA during ischemia. In addition, the present findings suggest that the renoprotective effect of l-carnosine on ischemic ARF is induced by its conversion to l-histidine and l-histamine and is mediated through the activation of histamine H 3 receptors in the central nervous system.

show abstract

mentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Renoprotective Effects of l-Carnosine on Ischemia/Reperfusion-Induced Renal Injury in Rats

Kurata¹,

Fujii²,

Tsutsui³

et al. 2006

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…Both Lactococcus lactis and L. helveticus express biochemically identical dipeptidases, PepDA (459 amino acids) and cytosol nonspecific dipeptidase EC 3.4.13.18 (474 amino acids), which are approximately 30% identical and 47% similar to RAP (11). These enzymes are biochemically distinct from RAP, are specific for dipeptides of variable composition, and have been isolated from the cytoplasm of prokaryotic cells (34,35).…”

Section: Discussionmentioning

confidence: 99%

Extracellular Arginine Aminopeptidase from Streptococcus gordonii FSS2

et al. 2002

View full text Add to dashboard Cite

Streptococcus gordonii is a primary etiological agent in the development of subacute bacterial endocarditis (SBE), producing thrombus formation and tissue damage on the surfaces of heart valves. This is ironic, considering its normal role as a benign inhabitant of the oral microflora. However, strain FSS2 of S. gordonii has been found to produce several extracellular aminopeptidase-and fibrinogen-degrading activities during growth in a pH-controlled batch culture. In this report, we describe the purification, characterization, and partial cloning of a predicted serine class arginine aminopeptidase (RAP) with some cysteine class characteristics. Isolation of this enzyme by anion-exchange, gel filtration, and isoelectric focusing chromatography yielded a protein monomer of approximately 70 kDa, as shown by matrix-assisted laser desorption ionization, gel filtration, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis under denaturing conditions. Nested-PCR cloning enabled the isolation of a 324-bp-long DNA fragment encoding the 108-amino-acid N terminus of RAP. Culture activity profiles and N-terminal sequence analysis indicated the export of this protein from the cell surface. Homology was found with a putative dipeptidase from Streptococcus pyogenes and nonspecific dipeptidases from Lactobacillus helveticus and Lactococcus lactis. We believe that RAP may serve as a critical factor for arginine acquisition during nutrient stress in vivo and also in the proteolysis of host proteins and peptides during SBE pathology.

show abstract

“…Although serum carnosinase activity has been well characterized (Lenney et al 1985;Pegova et al 2000;Dunnett et al 2002;Teufel et al 2003) using carnosine as a substrate, homocarnosine metabolism and the differential effects of the two primary substrates on CN1 activity have not been studied in detail. Furthermore, little is known concerning the relationship between carnosine and homocarnosine concentrations and CN1 activity in CSF.…”

Section: Introductionmentioning

confidence: 99%

Relevance of allosteric conformations and homocarnosine concentration on carnosinase activity

et al. 2009

View full text Add to dashboard Cite

Activity of carnosinase (CN1), the only dipeptidase with substrate specificity for carnosine or homocarnosine, varies greatly between individuals but increases clearly and significantly with age. Surprisingly, the lower CN1 activity in children is not reflected by differences in CN1 protein concentrations. CN1 is present in different allosteric conformations in children and adults since all sera obtained from children but not from adults were positive in ELISA and addition of DTT to the latter sera increased OD450 values. There was no quantitative difference in the amount of monomeric CN1 between children and adults. Further, CN1 activity was dose dependently inhibited by homocarnosine. Addition of 80 lM homocarnosine lowered V max for carnosine from 440 to 356 pmol/min/lg and increased K m from 175 to 210 lM. The estimated K i for homocarnosine was higher (240 lM). Homocarnosine inhibits carnosine degradation and high homocarnosine concentrations in cerebrospinal fluid (CSF) may explain the lower carnosine degradation in CSF compared to serum. Because CN1 is implicated in the susceptibility for diabetic nephropathy (DN), our findings may have clinical implications for the treatment of diabetic patients with a high risk to develop DN. Homocarnosine treatment can be expected to reduce CN1 activity toward carnosine, resulting in higher carnosine levels.

show abstract

Characterization of human tissue carnosinase

Cited by 108 publications

References 21 publications

Renoprotective Effects of l-Carnosine on Ischemia/Reperfusion-Induced Renal Injury in Rats

Renoprotective Effects of l-Carnosine on Ischemia/Reperfusion-Induced Renal Injury in Rats

Extracellular Arginine Aminopeptidase from Streptococcus gordonii FSS2

Relevance of allosteric conformations and homocarnosine concentration on carnosinase activity

Contact Info

Product

Resources

About