Serum Procalcitonin
Blood Tests

DEFINITION

Calcitonin

This family is formed by calcitonin, the calcitonin gene-related peptide, and amylin. They are short polypeptide hormones.
Interpro abstract (IPR001693):

Calcitonin (PUBMED:3060108) is a 32 amino acid polypeptide hormone that causes a rapid but short-lived drop in the level of calcium and phosphate in the blood, by promoting the incorporation of these ions in the bones, alpha type. Alternative splicing of the gene coding for calcitonin produces a distantly related peptide of 37 amino acids, called calcitonin gene-related peptide (CGRP), beta type. CGRP induces vasodilatation in a variety of vessels, including the coronary, cerebral and systemic vasculature. Its abundance in the CNS also points toward a neurotransmitter or neuromodulator role.

Islet amyloid polypeptide (IAPP) (PUBMED:2407732) (also known as diabetes-associated peptide (DAP), or amylin) is a peptide of 37 amino acids that selectively inhibits insulin-stimulated glucose utilization and glycogen deposition in muscle, while not affecting adipocyte glucose metabolism. Structurally, IAPP is closely related to CGRP.

Two conserved cysteines in the N-terminal of these peptides are known to be involved in a disulphide bond. The C-terminal residue of all three peptides is amidated.

xCxxxxxCxxxxxxxxxxxxxxxxxxxxxxxxxxxx-NH
| | Amide group
-----

CHEMICAL STRUCTURE AND IMAGES

When relevant for the function

• Primary structure
• Secondary structure
• Tertiary structure
  • PDB
• Quaternary structure

h4. Protein Aminoacids Percentage

The lack of Trp is shared by many inflammatory cytokines:

• TNF alpha
• IL-6

SYNTHESIS AND TURNOVER

mRNA synthesis

protein synthesis
post-translational modifications
degradation

CELLULAR FUNCTIONS

1. FUNCTION: Calcitonin causes a rapid but short-lived drop in the level of calcium and phosphate in blood by promoting the incorporation of those ions in the bones.
2. FUNCTION: Katacalcin is a potent plasma calcium-lowering peptide.
3. INTERACTION: P79222-1:CALCR (xeno); NbExp=1; IntAct=EBI-1018474, EBI-1188415;
4. SUBCELLULAR LOCATION: Secreted.
5. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=3; Name=1; IsoId=P01258-1; Sequence=Displayed; Name=2; IsoId=P01258-2; Sequence=VSP_000709; Note=May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay; Name=3; IsoId=P06881-1; Sequence=External;
6. SIMILARITY: Belongs to the calcitonin family.
7. WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/calca/";
8. WEB RESOURCE: Name=Wikipedia; Note=Calcitonin entry; URL="http://en.wikipedia.org/wiki/Calcitonin";

cellular localization,
biological function

Physiology and genetics of procalcitonin. 2000

High concentrations of procalcitonin but not mature calcitonin in normal human milk.
Horm Metab Res. 2002 Aug;34(8):460-5.
Struck J, de Almeida P, Bergmann A, Morgenthaler NG.

Research Laboratories, B.R.A.H.M.S AG, Biotechnology Center Hennigsdorf, Hennigsdorf, Germany.
Abstract

Procalcitonin (PCT) is one of the precursors in the synthesis of calcitonin in thyroidal C-cells and other neuroendocrine cells. PCT and other calcitonin precursors in serum are present at less than 50 pg/ml in healthy individuals, but are highly elevated in serum where conditions leading to systemic inflammatory response syndrome or sepsis prevail. We measured PCT concentrations in milk and serum samples taken from 9 healthy women after delivery. PCT concentrations were below 10 pg/ml in serum samples, but were more than 100 times as high in the corresponding milk samples. PCT in milk reached a maximum within the early days after delivery, with a median peak concentration of 2310 pg/ml (range 223 - 4224 pg/ml) at day one and 2442 pg/ml (range 952 - 4488 pg/ml) at day two, then declining over the next days to a median concentration of 747 pg/ml (range 443 - 1656 pg/ml) at day 10 (p = 0.012, by Friedman ANOVA). PCT values reached a steady state of 504 pg/ml median value. Mature calcitonin values measured in parallel with a specific assay were not above the normal range of 10 pg/ml in any samples measured. The strong discrepancy between serum and milk PCT suggests that PCT (but not mature calcitonin) is synthesised in the breast of healthy mothers after delivery. The precise mechanism and the physiological relevance are unclear. Since PCT levels increase drastically in serum from patients suffering from sepsis and related conditions, and since PCT has been ascribed a pro-inflammatory function, we propose that milk PCT might contribute to the activation of the developing neonatal immune system. Similar speculations were proposed for a variety of other pro-inflammatory cytokines, which had comparable kinetics in human milk.

• Enzymes
  • BRENDA - The Comprehensive Enzyme Information System
  • KEGG Pathways
  • Human Metabolome Database
• Cell signaling and Ligand transport
• Structural proteins

REGULATION

Scand J Infect Dis. 2010 Mar;42(3):164-71.
"Treatment with granulocyte-macrophage colony-stimulating factor is associated with reduced indoleamine 2,3-dioxygenase activity and kynurenine pathway catabolites in patients with severe sepsis and septic shock.":

Schefold JC, Zeden JP, Pschowski R, Hammoud B, Fotopoulou C, Hasper D, Fusch G, Von Haehling S, Volk HD, Meisel C, Schütt C, Reinke P.

Department of Nephrology and Intensive Care Medicine, Charité University Medicine, Campus Virchow, Berlin, Germany. schefold@charite.de
Abstract

The immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) controls tryptophan metabolism and is induced by pro-inflammatory stimuli. We investigated whether immunostimulatory treatment with granulocyte-macrophage colony-stimulating factor (GM-CSF) influences IDO activity and tryptophan metabolism in sepsis. Thirty-six patients with severe sepsis/septic shock and sepsis-associated immunosuppression (assessed using monocytic human leukocyte antigen-DR (mHLA-DR) expression) were assessed in a controlled trial of GM-CSF or placebo treatment for 8 days. Using tandem mass spectrometry, levels of tryptophan, kynurenine, kynurenic acid, quinolinic acid, 5-hydroxytryptophan, serotonin, and estimated IDO activity were determined in a blinded fashion over a 9-day interval. At baseline, tryptophan and metabolite levels did not differ between the study groups. Although tryptophan levels were unchanged in both groups over the treatment interval (all p>0.8), IDO activity was markedly reduced after GM-CSF treatment (35.4 +/- 21.0 vs 21.6 +/-9.9 (baseline vs day 9), p = 0.02). IDO activity differed significantly between the 2 groups after therapy (p = 0.03). Metabolites downstream of IDO (kynurenine, quinolinic acid, kynurenic acid) were all induced in sepsis and declined in the GM-CSF group, but not in controls. Serotonin pathway metabolites remained unchanged in both groups (all p>0.15). Moreover, IDO activity correlated with procalcitonin (p< 0.0001, r = 0.56) and mHLA-DR levels (p = 0.005, r = -0.28) in the overall samples group. Thus, GM-CSF therapy is associated with decreased IDO activity and reduced kynurenine pathway catabolites in sepsis. This may be due to an improved antibacterial defence.

J Biol Chem. 2009 Apr 24;284(17):11059-69. Epub 2009 Mar 4.
Calcitonin, a regulator of the 25-hydroxyvitamin D3 1alpha-hydroxylase gene.

Zhong Y, Armbrecht HJ, Christakos S.

Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, New Jersey 07103, USA.
Abstract

Although parathyroid hormone (PTH) induces 25-hydroxyvitamin D(3) (25(OH)D(3)) 1alpha-hydroxylase (1alpha(OH)ase) under hypocalcemic conditions, previous studies showed that calcitonin, not PTH, has an important role in the maintenance of serum 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) under normocalcemic conditions. In this study we report that 1alpha(OH)ase transcription is strongly induced by calcitonin in kidney cells and indicate mechanisms that underlie this regulation. The transcription factor C/EBPbeta is up-regulated by calcitonin in kidney cells and results in a significant enhancement of calcitonin induction of 1alpha(OH)ase transcription and protein expression. Mutation constructs of the 1alpha(OH)ase promoter demonstrate the importance of the C/EBPbeta binding site at -79/-73 for activation of the 1alpha(OH)ase promoter by calcitonin. The SWI/SNF chromatin remodeling complex was found to cooperate with calcitonin in the regulation of 1alpha(OH)ase. Chromatin immunoprecipitation analysis showed that calcitonin recruits C/EBPbeta to the 1alpha(OH)ase promoter, and Re-chromatin immunoprecipitation analysis (sequential chromatin immunoprecipitations using different antibodies) showed that C/EBPbeta and BRG1, an ATPase that is a component of the SWI/SNF complex, bind simultaneously to the 1alpha(OH)ase promoter. These findings are the first to address the dynamics between calcitonin, C/EBPbeta, and SWI/SNF in the regulation of 1alpha(OH)ase and provide a mechanism, for the first time, for calcitonin induction of 1alpha(OH)ase. Because plasma calcitonin as well as 1,25(OH)(2)D(3) have been reported to be increased during pregnancy and lactation and in early development, these findings suggest a mechanism that may account, at least in part, for the increase in plasma 1,25(OH)(2)D(3) during these times of increased calcium requirement.
h3. DIAGNOSTIC USE