Structural characterization of a high-molecular-mass form of calcitonin [procalcitonin-(60–116)-peptide] and its corresponding <i>N</i>-terminal flanking peptide [procalcitonin-(1–57)-peptide] in a human medullary thyroid carcinoma

Conlon, J. M.; Grimelius, Lars; Thim, Lars

doi:10.1042/bj2560245

Cited by 31 publications

(9 citation statements)

References 28 publications

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“…Into the C cells, procalcitonin is cleaved into calcitonin, katacalcin and a proteic residue, and it is not released into the blood stream of healthy individuals [1]. PCT is known as a good biological diagnostic marker for severe sepsis, or septic shock in critically ill patients [2].…”

Section: Introductionmentioning

confidence: 99%

Procalcitonin in patients with acute coronary syndromes and cardiogenic shock submitted to percutaneous coronary intervention

et al. 2009

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Procalcitonin (PCT) is known to be a biological diagnostic marker for severe sepsis, or septic shock in critically ill patients. There are still contrasting data about a role of procalcitonin in patients with acute myocardial infarction or cardiogenic shock, and in those with acute coronary syndromes, that is, non-ST-elevation myocardial infarction or unstable angina. We evaluated plasma levels of procalcitonin and C-reactive protein (CRP) in 52 patients admitted to our intensive cardiac care unit (ICCU): 14 patients with cardiogenic shock (CS) following ST-elevation myocardial infarction (STEMI), 15 patients with uncomplicated ST-elevation myocardial infarction (STEMI), and 24 with non-ST-elevation myocardial infarction or unstable angina (NSTEMI/UA). In all patients, infective processes were excluded. Procalcitonin values were significantly higher in CS patients with respect to the other two subgroups (P < 0.001, P < 0.001) while CRP levels were higher than NSTEMI/UA patients (P < 0.001) but not with respect to STEMI patients (P = 0.063). No correlations were found in cardiogenic shock patients between CRP and PCT values (R = 0.02; P = 0.762, ns). Procalcitonin levels measured on ICCU admission are significantly higher in patients with cardiogenic shock following the acute myocardial infarction, and they are not correlated with those of CRP. The degree of myocardial ischemia (clinically indicated by the whole spectrum of ACS, from unstable angina to cardiogenic shock ST-elevation following myocardial infarction) and the related inflammatory-induced response are better reflected by CRP (which was positive in most acute cardiac care patients of all our subgroups), than by PCT which seems more reflective of a higher degree of inflammatory activation, being positive only in all CS patients.

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Section: Introductionmentioning

confidence: 99%

Procalcitonin in patients with acute coronary syndromes and cardiogenic shock submitted to percutaneous coronary intervention

et al. 2009

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“…Recently, a 7-kDa 57-residue amino-terminal proCT cleavage peptide, N-proCT, was identified in rat and human C cells (19,20). Like C-proCT, N-proCT is secreted in equimolar amounts with CT (19).…”

Section: Introductionmentioning

confidence: 99%

“…An early report on CproCT claimed calcium-lowering and antiresorptive skeletal actions synergistic with CT (15). Other investigators and subsequently even the original reporting group found no CT-like actions for C-proCT (17,18).Recently, a 7-kDa 57-residue amino-terminal proCT cleavage peptide, N-proCT, was identified in rat and human C cells (19,20). Like C-proCT, N-proCT is secreted in equimolar amounts with CT (19).…”

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confidence: 99%

Procalcitonin's amino-terminal cleavage peptide is a bone-cell mitogen.

Burns¹,

Forstrom²,

Friday³

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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The parafollicular-cell (C-cell) hormone calcitonin (CT) can preserve or even augment skeletal mass by inhibiting osteoclast-mediated bone resorption. The possibility of an additional anabolic skeletal influence has also been raised: C cells might, via CT or other secretory products, affect osteoblast-mediated bone formation. The 57-residue aminoterminal procalcitonin cleavage peptide, N-proCT, has recently been identified in human and rat C cells, where it is made and secreted in equimolar amounts with CT. The coelaboration of N-proCT and CT and N-proCT's sequence conservation during evolution prompted us to investigate the potential skeletal bioactivity of N-proCT. We found that synthetic human N-proCT, at nanomolar concentrations, stimulated proliferation of normal and neoplastic human osteoblasts. At maximally effective doses, human N-proCT caused more than a 100% increase above the control rate of DNA synthesis, an effect comparable to the maximal growth effect of insulin, a potent mitogen for osteoblasts. Human N-proCT exerted a similar maximal mitogenic effect in chicken osteoblast cultures but at 1000-fold greater concentrations than in human bonecell cultures. The bone-cell action of N-proCT was potentiated with insulin with a >200% increase in DNA synthesis at high insulin concentrations. In sharp contrast to these fridings for N-proCT, the other bioactive C-cell peptides, CT and somatostatin, showed no mitogenic effects in human or chicken osteoblast cultures. Our results indicate that the action of N-proCT on cultured bone cells is separate from and potentiated by insulin, a known growth factor. Unlike insulin and related growth factors such as insulin-like growth factor I, N-proCT is not mitogenic in skin fibroblast cultures. We propose that N-proCT is a C-cell hormone that promotes bone formation via stimulatory actions on osteoblasts and preosteoblasts.Calcitonin (CT) is a 32-amino-acid peptide hormone that in mammals is secreted mainly by thyroidal C cells (parafollicular cells). Although its precise role is disputed, CT's primary action is to inhibit bone resorption. This inhibitory action on osteoclasts has been considered the main mechanism for the protective and anabolic skeletal effects ascribed to CT (1-5). Several reports suggest that CT may also have a stimulatory effect on osteoblasts and their progenitors (6)(7)(8). While such diversity of CT effects could explain many of the anabolic skeletal effects associated with C-cell secretory activity, yet another explanation is suggested by recent findings in corticotropin (ACTH) biosynthesis. Non-ACTH peptides cogenerated during processing of the ACTH precursor show ACTH-related bioactivity that is distinct from but complementary to the role of ACTH in stress physiology (9,10). In a similar manner, C cells could exert anabolic skeletal effects via the non-CT secretory peptides cogenerated with CT during processing of procalcitonin (proCT).ProCT has been identified in fish, chickens, rats, and humans (11-13). In each species, proCT is -...

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“…Although IAPPl_37 was identified as the major constituent of amyloid in the extracted samples of pancreatic tissue [1], the presence of pro-IAPP (or other fragments of pro-IAPP) in amyloid could not be excluded. Incomplete processing of procalcitonin at both the C-and N-terminals has been implicated in the amyloidosis associated with medullary carcinomas of the thyroid [6,7].…”

Section: Resultsmentioning

confidence: 99%

Localisation of islet amyloid polypeptide and its carboxy terminal flanking peptide in islets of diabetic man and monkey

et al. 1991

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Islet amyloid polypeptide is a normal constituent of islet Beta cells and is derived from a larger precursor by removal of flanking peptides at the carboxy (C) and amino (N) terminals. The role of these flanking peptides in the formation of amyloid in Type 2 (non-insulin-dependent) diabetes mellitus and in insulinomas is unknown. The C-terminal flanking peptide of islet amyloid polypeptide was localised by immunocytochemistry in human and monkey pancreatic islets from Type 2 diabetic and non-diabetic individuals by use of specific polyclonal antisera. Immunoreactivity for the C-terminal peptide was found in insulin-containing cells in both diabetic and non-diabetic tissue: no antibody binding was detected in islet amyloid of Type 2 diabetic man or of monkeys although a positive reaction occurred with antisera for islet amyloid polypeptide. The C-terminal peptide was localised by immunogold electron microscopy in the insulin granules in both diabetic and non-diabetic individuals but, unlike islet amyloid polypeptide, was not detected in lysosomes. The absence of immunoreactivity for the C-terminal peptide in amyloid suggests that incomplete cleavage of this flanking peptide from islet amyloid polypeptide is not a factor in the formation of islet amyloid.

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Structural characterization of a high-molecular-mass form of calcitonin [procalcitonin-(60–116)-peptide] and its corresponding N-terminal flanking peptide [procalcitonin-(1–57)-peptide] in a human medullary thyroid carcinoma

Cited by 31 publications

References 28 publications

Procalcitonin in patients with acute coronary syndromes and cardiogenic shock submitted to percutaneous coronary intervention

Procalcitonin in patients with acute coronary syndromes and cardiogenic shock submitted to percutaneous coronary intervention

Procalcitonin's amino-terminal cleavage peptide is a bone-cell mitogen.

Localisation of islet amyloid polypeptide and its carboxy terminal flanking peptide in islets of diabetic man and monkey

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