Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the production of parathyroid hormone-related protein (PTHrP) by cells derived from explants of human bone. Using an immunoradiometric assay (IRMA), PTHrP was detected in conditioned medium from cultures of bone-derived cells from 6 of 7 patients investigated in this study. PTHrP mRNA was identified in human bone cells using reverse transcriptase-linked polymerase chain reaction (RT-PCR) and by Northern analysis. Transcripts for PTHrP were detected in a purified population of alkaline phosphatase positive cells isolated from human bone marrow cultures by flow cytometry, confirming the expression of PTHrP mRNA by cells of the osteoblastic lineage. Production of PTHrP was inhibited by 10(-6) M of the glucocorticoids, prednisolone and desacetylated deflazacort, in a dose-dependent manner. In addition, RT-PCR followed by Southern blot analysis detected a decrease in steady-state PTHrP mRNA in cultures of human bone-derived cells treated with 10(-6) M prednisolone.
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PMID:Expression and secretion of parathyroid hormone-related protein by human bone-derived cells in vitro: effects of glucocorticoids. 774 25

Parathyroid hormone-related protein (PTHrP) is synthesized by a variety of tumors and is thought to be the main cause of the clinical syndrome of humoral hypercalcemia of malignancy (HHM). In addition to its parathyroid hormone (PTH)-like actions, novel actions of PTHrP on placental calcium transport and inhibition of in vitro osteoclast activity have been demonstrated. The fact that osteoblasts act as mediators of osteoclastic bone resorption prompted us to investigate whether nontranformed, osteoblastlike cells produce PTHrP. PTHrP has been detected in developing human fetal bones and in rat long bones in culture. For this study, osteogenic cells, CRP 5/4 and CRP 10/30, were employed. Both cell types represent clonal bone cell populations established from 1-day-old rats. While CRP 10/30 cells express the osteoblastic phenotype, CRP 5/4 cells resemble cells with preosteoblastic properties. With a radioimmunoassay (RIA), utilizing antiserum directed against the amino-terminal PTHrP(1-40), it was found that both cell types synthesize PTHrP constitutively. CRP 10/30 cells produce about twice as much as CRP 5/4 cells. Transforming growth factor-beta (TGF-beta 1) was shown to increase the synthesis of PTHrP in CRP 5/4 cells by about 2.5-fold, while in CRP 10/30 cells it caused an approximate 50% reduction of PTHrP. Employing the reverse transcriptase polymerase chain reaction (RT-PCR) technique it was found that both bone cell types express mRNA for PTHrP and that the modulation of the PTHrP mRNA levels by TGF-beta 1 in CRP 5/4, and to a lesser degree in CRP 10/30 cells, was reflected in a change in the level of PTHrP protein in the culture medium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evidence for the synthesis of parathyroid hormone-related protein (PTHrP) by nontransformed clonal rat osteoblastic cells in vitro. 778 37

Parathyroid hormone-related protein (PTHrP), a mediator of hypercalcemia of malignancy, has been detected in many tumours and in some normal foetal and adult tissues. PTHrP has potent effects on bone turnover in vivo and in vitro. In this study we cultured cells derived from explants of bone obtained from 40 subjects (age range 2-88 years). Immunoreactive PTHrP (iPTHrP) was detected by immunoradiometric assay (IRMA) in conditioned medium from 25 of 40 cultures of bone-derived cells. PTHrP mRNA was detected in bone-derived cells by reverse transcriptase-linked polymerase chain reaction (RT-PCR). The identity of PCR products was confirmed by Southern blotting. Local production of PTHrP in vivo may be important in the regulation of bone growth and remodelling.
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PMID:Primary cultures of human bone-derived cells produce parathyroid hormone-related protein: a study of 40 patients of varying age and pathology. 784 45

PTH-related peptide (PTHrP), the factor mediating the syndrome of humoral hypercalcemia of malignancy, is also expressed in smooth muscle cells (SMC) of the urinary bladder and uterus in response to mechanical distention and fetal occupancy, respectively. Vascular SMC also produce PTHrP, and its expression is induced by serum and vasoconstrictors, such as angiotensin-II. To determine whether mechanical distension affected vascular PTHrP gene expression, the abdominal aorta of adult male rats was balloon-distended, and aortae were collected at various times after the intervention. PTHrP mRNA was determined by competitive reverse transcriptase-polymerase chain reaction, using sequential dilutions of a cloned internally truncated PTHrP RNA fragment as standard. The molar concentration of PTHrP mRNA was obtained by extrapolating at a standard/wild-type band intensity ratio of 1:1. Aortic PTHrP mRNA was induced from a basal level of 19, to 22, 46, 36, 13, 12, 22, and 20 attamoles/mg total RNA 1, 2, 12, 24, and 48 h and 7 and 48 days after balloon distension, respectively. To determine whether mechanical events directly regulate vascular PTHrP gene expression, primary rat aortic SMC were plated and placed on a rocking device at 20 oscillations/min to create a gentle flowing motion of the culture medium. Rocking induced PTHrP mRNA of SMC exposed to either serum-free medium or 10% serum by 2.5-and 4.0-fold at 4 h, and 2.9- and 3.7-fold at 24 h, respectively. These effects were oscillation rate dependent, potentiated by angiotensin-II, and specific, as similar changes were not observed in alpha-actin mRNA content. Flow motion-induced PTHrP mRNA at 24 h was partially decreased by 10(-6) M colchicine (which inhibits microtubule assembly), but not by cytochalasin-E (which disrupts actin polymerization). As PTHrP is a known vasorelaxant, we propose that mechanical events induce the release of PTHrP by SMC, possibly to serve as a compliance factor or an agent for vascular remodeling.
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PMID:Mechanical stimuli induce vascular parathyroid hormone-related protein gene expression in vivo and in vitro. 815 26

Parathyroid hormone-related protein is responsible for the hypercalcaemia caused by many tumours. Measurement of parathyroid hormone-related protein is becoming more accessible with the introduction of commercial assays. We report a case of hypercalcaemia of malignancy secondary to parathyroid hormone-related protein in a woman with renal carcinoma. The parathyroid hormone-related protein was assayed using a new immunoradiometric assay. We demonstrated an initial fall in parathyroid hormone-related protein and calcium levels after surgery and a rise in both before clinical relapse. However, the clinical relapse was itself associated with a fall in serum parathyroid hormone-related protein, nephrogenous cAMP and calcium, suggesting that the tumour had stopped producing parathyroid hormone-related protein or perhaps that post-translational processing had occurred as the tumour advanced. The tumour was investigated for parathyroid hormone-related protein mRNA content using reverse transcriptase polymerase chain reaction, both at diagnosis in surgically removed material, and using post-mortem specimens. The level of parathyroid hormone-related protein mRNA, while present, was much reduced in the recurrent tumour suggesting that active parathyroid hormone-related protein production fell substantially as the tumour advanced. This case suggests that, although demonstration of parathyroid hormone-related protein in hypercalcaemia is useful for diagnosis, tumoral secretion of this product may alter.
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PMID:Hypercalcaemia due to parathyroid hormone-related protein: long-term circulating levels may not reflect tumour activity. 828 89

Alveolar epithelial cells in vivo, primary cultures of adult rat type II cells, and human A549 alveolar carcinoma cells express parathyroid hormone-related protein (PTHrP). Here we demonstrated that type II cells and A549 cells also express the PTHrP receptor and that they exhibit differentiation-related responses to the amino-terminal PTHrP fragment, PTHrP-(1-34). PTHrP receptor expression in A549 cells was shown by detection of a 0.3-kb reverse transcriptase polymerase chain reaction product formed by primers specific for PTHrP receptor. In situ hybridization studies localized the site of production of PTHrP and PTHrP receptor mRNA in rat lung cells with morphology and location typical of type II cells. Primary cultures of such type II cells also expressed PTHrP receptor mRNA. Incubation with PTHrP-(1-34) stimulated disaturated phosphatidylcholine (DSPC) synthesis in A549 cells and increased the release of newly synthesized DSPC by cultured type II cells and A549 cells. In addition, PTHrP-(1-34) increased the number of lamellar bodies per type II cell and increased their expression of alkaline phosphatase in a dose-dependent manner. Thus PTHrP-(1-34) promoted a differentiated type II cell phenotype. Since cultured type II cells, alveolar epithelial cells in vivo, and A549 cells express PTHrP and the PTHrP receptor, PTHrP-(1-34) may be an autocrine regulatory factor in type II cells and lung cancer cells.
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PMID:Parathyroid hormone-related protein, an autocrine regulatory factor in alveolar epithelial cells. 863 27

We used differential display of mRNA, a method based on reverse transcriptase-PCR, to identify genes whose expression increases in response to acoustic trauma in the chick basilar papilla. Identifying these genes would provide insight into processes involved in repair of the damaged epithelium or in hair cell regeneration. We compared mRNA from the basilar papilla of normal chicks, from chicks exposed to an octave band noise (center frequency: 1.5 kHz) presented at 118 dB for 6 h, and from chicks exposed to noise and allowed to recover for 2 days. Thus far, we have identified 70 bands that appear to be differentially displayed on DNA sequencing gels; approximately 40 of these bands have been subcloned and sequenced. DNA sequences were compared with sequences in the GenBank database to identify genes with significant (70-85%) sequence identity to known genes. Chick cDNAs identified included: the parathyroid hormone-related protein, an immediate early gene; the delta-subunit of the neuronal-specific Ca2+/calmodulin-regulated protein kinase II; and the GTP-binding protein CDC42, a member of the ras superfamily of G proteins. A fourth cDNA had 84% sequence identity to an uncharacterized human cDNA (expressed sequence tag), indicating that this is a novel gene. Slot-blot hybridization analysis of these cDNAs probed with labeled DNA generated from mRNA from each experimental group indicated higher levels of mRNA for each of these four genes after noise exposure. These results indicate the potential involvement of both Ca2+/calmodulin-mediated signaling and GTPase cascades in the response to noise damage and during hair cell regeneration in the chick basilar papilla.
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PMID:Identification of genes expressed after noise exposure in the chick basilar papilla. 881 3

Using a strategy based on homology to the bovine parathyroid Ca(2+)-sensing receptor previously identified by us (5), we have recently isolated an extracellular, G protein-coupled Ca2+/ polyvalent cation-sensing receptor, RaKCaR (22), from rat kidney. The localization and physiological role(s) of this receptor in the kidney are not well understood. In the present study, we assessed the distribution of mRNAs for RaKCaR and the parathyroid hormone/parathyroid hormone-related protein (PTH/PTHrP) receptor along the rat nephron by in situ hybridization and reverse transcriptase-polymerase chain reaction of microdissected nephron segments. Our results show that transcripts for both receptors coexpress at glomeruli, proximal convoluted tubule, proximal straight tubule, cortical thick ascending limb, distal convoluted tubule, and cortical collecting duct. In addition, RaKCaR (but not PTH/PTHrP receptor) transcripts were found in the medullary thick ascending limb and outer medullary and inner medullary collecting ducts. These findings raise the possibility of roles for RaKCaR not only in the regulation of divalent mineral reabsorption but also in water reabsorption and urinary concentration. Taken together, our results provide new insights in understanding the effects of hypercalcemia on hormone-stimulated salt and water transport.
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PMID:Localization of the extracellular Ca(2+)-sensing receptor and PTH/PTHrP receptor in rat kidney. 889 27

Cancers from patients with tumor-induced hypercalcemia usually produce a circulating factor that mimics the parathyroid hormone activity, termed parathyroid hormone-related protein. Incidence of tumor-induced hypercalcemia appears to be high in patients with squamous cell carcinoma of the esophagus, and the presence of parathyroid hormone-related protein have been shown in some primary esophageal cancers. In the present study, we have investigated the presence of parathyroid hormone-related protein in a patient with metastasized squamous cell carcinoma of the esophagus complicated with tumor-induced hypercalcemia. Protein was searched by immunohistochemistry, and messenger RNA was investigated by reverse transcriptase-polymerase chain reaction and S1 nuclease assay. Both messenger RNA and protein were detected in hepatic metastases, whereas normal esophageal mucosa and primary cancer did not express detectable protein or messenger RNA using the S1 nuclease assay. Reverse transcriptase-polymerase chain reaction was positive in all these tissues, including normal esophageal mucosa. In conclusion, the present case suggests that tumor-induced hypercalcemia due to esophageal squamous cell carcinoma may be caused by parathyroid hormone-related protein mostly released by liver metastases.
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PMID:Parathyroid hormone-related protein in an esophageal squamous cell carcinoma with tumor-induced hypercalcemia. 904 Feb 21

PTH-related protein (PTHrP) is found in a variety of tissues; particularly high levels are present in human milk. The structure of the human PTHrP gene is complex, and alternative splicing allows expression of three different variants PTHrP139, PTHrP173, and PTHrP141, respectively. To determine which of the variants are expressed in human mammary gland a reverse transcriptase polymerase chain reaction (RT-PCR) method was elaborated, distinguishing the three variants. mRNA isolated from human milk cells, human mammary epithelial cells (HMEC) and human nonlactating mammary gland cells were analyzed. The RT-PCR experiments resulted in amplification of DNA fragments corresponding to all three variants for all three cell sources tested. The nucleotide sequences of the PCR fragments were determined and verified to be identical to the reported sequences. Hence, it is concluded that human mammary gland epithelial cells express three variants of PTHrP. Whether these have different physiologic effects in the mammary gland or in the breast fed infant remain to be explored.
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PMID:Three variants of parathyroid hormone-related protein messenger RNA are expressed in human mammary gland. 907 39


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