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Intrinsic carnosine metabolism in the human kidney.

Peters V, Klessens CQ, Baelde HJ, Singler B, Veraar KA, Zutinic A, Drozak J, Zschocke J, Schmitt CP, de Heer E - Amino Acids (2015)

Bottom Line: Finally, TauT mRNA and protein were found in all renal epithelial cells.Both CNDP1 and CARNS are expressed in glomeruli and tubular cells.Carnosine-synthesizing and carnosine-hydrolyzing enzymes are localized in distinct compartments in the nephron and increased CNDP1 levels suggest a higher CNDP1 activity in diabetic kidneys.

View Article: PubMed Central - PubMed

Affiliation: University Children's Hospital, University of Heidelberg, Im Neuenheimer Feld 672, 69120, Heidelberg, Germany.

ABSTRACT
Histidine-containing dipeptides like carnosine and anserine have protective functions in both health and disease. Animal studies suggest that carnosine can be metabolized within the kidney. The goal of this study was to obtain evidence of carnosine metabolism in the human kidney and to provide insight with regards to diabetic nephropathy. Expression, distribution, and localization of carnosinase-1 (CNDP1), carnosine synthase (CARNS), and taurine transporters (TauT) were measured in human kidneys. CNDP1 and CARNS activities were measured in vitro. CNDP1 and CARNS were located primarily in distal and proximal tubules, respectively. Specifically, CNDP1 levels were high in tubular cells and podocytes (20.3 ± 3.4 and 15 ± 3.2 ng/mg, respectively) and considerably lower in endothelial cells (0.5 ± 0.1 ng/mg). CNDP1 expression was correlated with the degradation of carnosine and anserine (r = 0.88 and 0.81, respectively). Anserine and carnosine were also detectable by HPLC in the renal cortex. Finally, TauT mRNA and protein were found in all renal epithelial cells. In diabetic patients, CNDP1 seemed to be reallocated to proximal tubules. We report compelling evidence that the kidney has an intrinsic capacity to metabolize carnosine. Both CNDP1 and CARNS are expressed in glomeruli and tubular cells. Carnosine-synthesizing and carnosine-hydrolyzing enzymes are localized in distinct compartments in the nephron and increased CNDP1 levels suggest a higher CNDP1 activity in diabetic kidneys.

No MeSH data available.


Related in: MedlinePlus

CDNP1 mRNA was amplified from human kidney samples (1.00 ± 1.12) (N = 8), human glomeruli (Glom) (0.802 ± 1.1) (N = 8), immortalized human podocytes (0.016 ± 0.0013) (N = 2), human endothelial cells (HUVEC) (0.001 ± 0.0013) (N = 5), and human proximal tubular epithelial cells (HK2 cells) (0.000185) (N = 1). All values were normalized to the mean value obtained from the human kidney samples. Note that the y-axis is plotted on a logarithmic scale, expressed as mean ± SD of relative units
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Fig2: CDNP1 mRNA was amplified from human kidney samples (1.00 ± 1.12) (N = 8), human glomeruli (Glom) (0.802 ± 1.1) (N = 8), immortalized human podocytes (0.016 ± 0.0013) (N = 2), human endothelial cells (HUVEC) (0.001 ± 0.0013) (N = 5), and human proximal tubular epithelial cells (HK2 cells) (0.000185) (N = 1). All values were normalized to the mean value obtained from the human kidney samples. Note that the y-axis is plotted on a logarithmic scale, expressed as mean ± SD of relative units

Mentions: Immunohistochemistry showed that the CNDP1 protein is localized primarily in the distal tubules and in the glomeruli (Fig. 1a). Next, we measured the mRNA levels, protein levels, and enzyme activity of CNDP1 in human kidney samples and cultured cells. The relative transcription levels were highest in the human kidney (1.00 ± 1.12 relative units), glomeruli (0.802 ± 1.1), whereas extremely low levels of CNDP1 mRNA were detected in HUVEC cells (0.001 ± 0.0013) and HK2 cells (0.000185) (Fig. 2). In immortalized podocytes the relative transcription was also high (0.016 ± 0.013). Consistent with this rank order of CNDP1 expression, CNDP1 protein levels were high in immortalized podocytes (15 ± 3.2 ng/mg protein) and low in HUVEC cells (0.5 ± 0.1 ng/mg protein); interestingly, CNDP1 protein levels were high in HK2 cells (20.3 ± 3.4 ng/mg protein). CNDP1 activity reflected high catabolic rates of carnosine and anserine in podocytes (2.8 ± 1.7 and 2.9 ± 1.5 nmol/mg/h, respectively) and tubular cells (2.6 ± 0.2 and 3.9 ± 0.4 nmol/mg/h, respectively) and low carnosine and anserine catabolic rates in HUVEC cells (1.3 ± 0.4 and 0.05 ± 0.08 nmol/mg/h, respectively) (Fig. 3). Both, CNDP1 protein levels and CNDP1 enzyme activities were correlated to carnosine (r = 0.88) and anserine (r = 0.81) degradation.Fig. 1


Intrinsic carnosine metabolism in the human kidney.

Peters V, Klessens CQ, Baelde HJ, Singler B, Veraar KA, Zutinic A, Drozak J, Zschocke J, Schmitt CP, de Heer E - Amino Acids (2015)

CDNP1 mRNA was amplified from human kidney samples (1.00 ± 1.12) (N = 8), human glomeruli (Glom) (0.802 ± 1.1) (N = 8), immortalized human podocytes (0.016 ± 0.0013) (N = 2), human endothelial cells (HUVEC) (0.001 ± 0.0013) (N = 5), and human proximal tubular epithelial cells (HK2 cells) (0.000185) (N = 1). All values were normalized to the mean value obtained from the human kidney samples. Note that the y-axis is plotted on a logarithmic scale, expressed as mean ± SD of relative units
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4633449&req=5

Fig2: CDNP1 mRNA was amplified from human kidney samples (1.00 ± 1.12) (N = 8), human glomeruli (Glom) (0.802 ± 1.1) (N = 8), immortalized human podocytes (0.016 ± 0.0013) (N = 2), human endothelial cells (HUVEC) (0.001 ± 0.0013) (N = 5), and human proximal tubular epithelial cells (HK2 cells) (0.000185) (N = 1). All values were normalized to the mean value obtained from the human kidney samples. Note that the y-axis is plotted on a logarithmic scale, expressed as mean ± SD of relative units
Mentions: Immunohistochemistry showed that the CNDP1 protein is localized primarily in the distal tubules and in the glomeruli (Fig. 1a). Next, we measured the mRNA levels, protein levels, and enzyme activity of CNDP1 in human kidney samples and cultured cells. The relative transcription levels were highest in the human kidney (1.00 ± 1.12 relative units), glomeruli (0.802 ± 1.1), whereas extremely low levels of CNDP1 mRNA were detected in HUVEC cells (0.001 ± 0.0013) and HK2 cells (0.000185) (Fig. 2). In immortalized podocytes the relative transcription was also high (0.016 ± 0.013). Consistent with this rank order of CNDP1 expression, CNDP1 protein levels were high in immortalized podocytes (15 ± 3.2 ng/mg protein) and low in HUVEC cells (0.5 ± 0.1 ng/mg protein); interestingly, CNDP1 protein levels were high in HK2 cells (20.3 ± 3.4 ng/mg protein). CNDP1 activity reflected high catabolic rates of carnosine and anserine in podocytes (2.8 ± 1.7 and 2.9 ± 1.5 nmol/mg/h, respectively) and tubular cells (2.6 ± 0.2 and 3.9 ± 0.4 nmol/mg/h, respectively) and low carnosine and anserine catabolic rates in HUVEC cells (1.3 ± 0.4 and 0.05 ± 0.08 nmol/mg/h, respectively) (Fig. 3). Both, CNDP1 protein levels and CNDP1 enzyme activities were correlated to carnosine (r = 0.88) and anserine (r = 0.81) degradation.Fig. 1

Bottom Line: Finally, TauT mRNA and protein were found in all renal epithelial cells.Both CNDP1 and CARNS are expressed in glomeruli and tubular cells.Carnosine-synthesizing and carnosine-hydrolyzing enzymes are localized in distinct compartments in the nephron and increased CNDP1 levels suggest a higher CNDP1 activity in diabetic kidneys.

View Article: PubMed Central - PubMed

Affiliation: University Children's Hospital, University of Heidelberg, Im Neuenheimer Feld 672, 69120, Heidelberg, Germany.

ABSTRACT
Histidine-containing dipeptides like carnosine and anserine have protective functions in both health and disease. Animal studies suggest that carnosine can be metabolized within the kidney. The goal of this study was to obtain evidence of carnosine metabolism in the human kidney and to provide insight with regards to diabetic nephropathy. Expression, distribution, and localization of carnosinase-1 (CNDP1), carnosine synthase (CARNS), and taurine transporters (TauT) were measured in human kidneys. CNDP1 and CARNS activities were measured in vitro. CNDP1 and CARNS were located primarily in distal and proximal tubules, respectively. Specifically, CNDP1 levels were high in tubular cells and podocytes (20.3 ± 3.4 and 15 ± 3.2 ng/mg, respectively) and considerably lower in endothelial cells (0.5 ± 0.1 ng/mg). CNDP1 expression was correlated with the degradation of carnosine and anserine (r = 0.88 and 0.81, respectively). Anserine and carnosine were also detectable by HPLC in the renal cortex. Finally, TauT mRNA and protein were found in all renal epithelial cells. In diabetic patients, CNDP1 seemed to be reallocated to proximal tubules. We report compelling evidence that the kidney has an intrinsic capacity to metabolize carnosine. Both CNDP1 and CARNS are expressed in glomeruli and tubular cells. Carnosine-synthesizing and carnosine-hydrolyzing enzymes are localized in distinct compartments in the nephron and increased CNDP1 levels suggest a higher CNDP1 activity in diabetic kidneys.

No MeSH data available.


Related in: MedlinePlus