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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcium-activated neutral protease activity was detected in mouse MC3T3-E1 cell extracts. Inclusion of the cysteine protease inhibitor, E64c, reduced the activity, while pretreatment of intact cells with 10 nM parathyroid hormone for 90 minutes increased it. The presence of calpains in solubilized cells was confirmed by Western blotting using an antibody specific for the 80 K catalytic subunit. These results, combined with the observation that preincubation with a membrane-permeable cysteine protease inhibitor ablates 50% of the PTH-induced osteoblastic retraction, suggest that calpain-catalyzed hydrolysis of regulatory enzymes or structural proteins plays a role in mediating its short-term effects in bone.
Biochem Mol Biol Int 1993 Apr
PMID:Identification of calcium-activated neutral protease activity and regulation by parathyroid hormone in mouse osteoblastic cells. 850 48

To evaluate the role of parathyroids in calculus disease, the parathyroid hormone levels were determined in 22 control subjects and 42 stone (14 with bladder stone and 28 with kidney stone) patients. Serum calcium, inorganic phosphate, alkaline phosphatase and parathyroid hormone and urinary excretion of calcium and inorganic phosphate were determined. It was found that normocalcemic and normocalciuric stone patients had slightly higher levels of parathyroid hormone (irrespective of the site of the stone) and the difference was not statistically significant as compared with control subjects although some of the patients with calculus disease were hyperparathyroid. Serum alkaline phosphatase was increased while there was an increase in urinary calcium excretion in kidney stone patients and oxalate in all patients as compared with control subjects. The increase in inorganic phosphate was, however, not different from the control subjects. The subclinical hyperparathyroidism and stone formation in these patients are not correlated.
Mol Cell Biochem 1993 Apr 07
PMID:Parathyroid hormone in urinary stone patients. 851 Jun 69

A binemic model of eukaryotyc chromosome was tested using PCR-amplification of some unique genes in individual sperm cells or in human DNA diluted to 1/2 of the DNA amount of a haploid cell. According to the model, all the hereditary information, including all the unique genes, is represented twice in the haploid genome. Backing up of information enhances reliability of the genome by several orders of magnitude. Hemoglobin G gene (HBG2) and parathyroid hormone gene (PTH) were studied. In the first experimental plot the DNA from one isolated spermatozoon was divided into 4 parts and G globin gene was attempted to be amplified in all 4 tubes. According to the binemic model the simultaneous positive reaction in a pair of tubes should occur in up to 75% of cases and the reaction in only one tube from the four should occur in the case of uninemy. In the second approach, human DNA was serially deluted to the 1/2 of the haploid genome per tube. After amplification, the number of tubes with positive signal were counted. According to the unineme model, 3.7 positive reactions from 10 were expected. According to the bineme model 6.3 positive reactions from 10 should be observed (as follows from Poisson distribution). The results obtained with both methods are in accordance with binemic model and are inconsistent with uninemy.
Biochem Mol Biol Int 1995 Jul
PMID:Experimental evidence for the binemic structure of human chromosomes. 852 35

Our studies suggest that protein kinase C is involved in low calcium (Ca2+)-stimulated secretion of parathyroid hormone (PTH) but not directly in high Ca(2+)-stimulated intracellular degradation of PTH to secreted carboxyl-terminal fragments (C-PTH), an important component of Ca(2+)-regulated PTH secretion. The present study was undertaken to determine the presence of calcium-activated proteases, 84 kDa (micro)-calpain and 80 kDa (milli)-calpain, in the bovine parathyroid, and whether they could degrade PTH to C-terminal fragments. Immunocytochemistry of bovine parathyroid tissue using antibodies raised against bovine heart micro- and milli-calpain detected both isoforms of calpain. Western blotting of total bovine parathyroid cell protein prepared from primary cell cultures confirmed the presence of both isoforms of calpain, demonstrated by specific milli- and micro-calpain bands. Purified bovine PTH (bPTH) was incubated in vitro with human erythrocyte micro-calpain and the cleavage products were separated by reverse-phase HPLC. Eluant fractions were assayed with an RIA with equimolar sensitivity to C-PTH and bPTH, and peak areas integrated. Micro-calpain produced a C-PTH peak from bPTH which co-eluted with the major C-PTH secreted by parathyroid cells in culture. C-PTH production by micro-calpain, expressed as per cent area under the curve, increased from 0% in the absence of either micro-calpain or Ca2+, to 71.5% when a 5:1 molar ratio of bPTH to calpain was used. Amino acid sequencing and analysis of the immunoreactive PTH cleavage products indicated the presence of two fragments of bPTH in the C-PTH peak, bPTH47-48 and bPTH69-84. In summary, both isoforms of calpain are present in the bovine parathyroid and calpains may play a role in the Ca(2+)-dependent degradation of PTH to secreted C-terminal fragments.
J Mol Endocrinol 1995 Aug
PMID:Calcium-activated proteases in the bovine parathyroid gland: potential role in degradation of parathyroid hormone to peptide fragments. 854 14

The effects of alpha 2-adrenergic receptors are usually attributed to inhibition of adenylyl cyclase through pertussis toxin-sensitive Gi coupling. In kidney distal convoluted tubule (DCT) cells, stimulation of Na+/K(+)-ATPase by alpha 2 receptors involves activation of protein kinase C (PKC). To identify the signal pathways coupled to alpha 2 receptors, we measured cAMP production and show that the alpha 2 agonist B-HT 933 had no effect on basal or stimulated (forskolin, parathyroid hormone) cAMP accumulation in DCT cells but inhibited parathyroid hormone-stimulated cAMP accumulation in proximal tubule cells. I tested whether alpha 2 receptors on DCT cells stimulate PKC through second messengers generated from phospholipase C (PLC) activation. In DCT cells, B-HT 933 increased inositol-1,4,5-trisphosphate formation by 4-6-fold over control and increased diacylglycerol formation by 46%. Basal intracellular calcium concentration in single DCT cells averaged 114 nM and increased within 2 min to 196 nM with B-HT 933. Treatment with the PLC inhibitor U-73122 but not pertussis toxin blocked B-HT 933-induced rises in inositol-1,4,5-trisphosphate and intracellular calcium concentration. B-HT 933 increased PKC activity by 45% over control in DCT cells. These findings provide evidence that alpha 2-adrenergic receptors activate PLC in DCT cells through a pertussis toxin-insensitive mechanism.
Mol Pharmacol 1996 Aug
PMID:Alpha 2-adrenergic receptors activate phospholipase C in renal epithelial cells. 870 Jan 50

Due to the importance of Ca2+ in the regulation of vital cellular and tissue functions, the concentration of Ca2+ in body fluids is closely guarded by an efficient feedback control system. This system includes Ca(2+)-transporting subsystems (bone, and kidney), Ca2+ sensing, possibly by a calcium-sensing receptor, and calcium-regulating hormones (parathyroid hormone [PTH], calcitonin [CT], and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]). In humans and birds, acute Ca2+ perturbations are handled mainly by modulation of kidney Ca2+ reabsorption and by bone Ca2+ flow under PTH and possibly CT regulation, respectively. Chronic perturbations are also handled by the more sluggish but economic regulatory action of 1,25(OH2)D3 on intestinal calcium absorption. Peptide hormone secretion is modulated by Ca2+ and several secretagogues. The hormones' signal is produced by interaction with their respective receptors, which evokes the cAMP and phospholipase C-IP3-Ca2+ signal transduction pathways. 1,25 (OH)2D3 operates through a cytoplasmic receptor in controlling transcription and through a membrane receptor that activates the Ca2+ and phospholipase C messenger system. The calciotropic hormones also influence processes not directly associated with Ca2+ regulation, such as cell differentiation, and may thus affect the calcium-regulating subsystems also indirectly.
Crit Rev Biochem Mol Biol 1996 Feb
PMID:Homeostatic control of plasma calcium concentration. 874 55

We compared the expression of osteoblastic markers in cultured human cells isolated from fracture calluses of various histological states of development with that in cells from adult and fetal bone. Adult osteoblasts and all callus cells produced almost exclusively type I collagen, whereas fetal osteoblasts produced also considerable amounts of type III collagen in vitro. 1,25-Dihydroxyvitamin D3 induced the synthesis of osteocalcin in all bone and callus cells but to varying extents. Fetal bone cells and early-stage callus cells synthesized less than 10% the amount of osteocalcin produced by adult bone cells. Late-stage callus cells produced intermediate levels of osteocalcin. Fetal bone cells and early-stage callus cells responded to parathyroid hormone with a less pronounced increase in intracellular cAMP than did adult bone cells. Late-stage callus cells showed the best response to parathyroid hormone. The activity of alkaline phosphatase was highest in fetal bone cells. These observations show that cells isolated from fetal bone and from fracture callus tissues express a pattern of markers clearly relating them to the osteoblastic lineage. On the basis of the different patterns of osteoblastic markers expressed in vitro we conclude that functionally distinct subtypes of osteoblasts do exist in different mineralized tissues and at different developmental stages.
J Mol Med (Berl) 1995 Nov
PMID:Expression of osteoblastic markers in cultured human bone and fracture callus cells. 875 Nov 41

The effect of zinc compounds on osteoclast-like cell formation in rat marrow culture in vitro was investigated. The bone marrow cells were cultured for 7 days in alpha-minimal essential medium containing a well-known bone resorbing hormone (1, 25-dihydroxyvitamin D3 and parathyroid hormone [1-34]). Osteoclast-like cell formation was estimated by staining for tartrate-resistant acid phosphatase (TRACP), a marker enzyme of osteoclasts. The presence of 1, 25-dihydroxyvitamin D3 (10(-8) M) or parathyroid hormone (PTH; 10(-8) M) induced a remarkable increase in osteoclast-like multinucleated cells (MNC). These increases were clearly inhibited by the presence of zinc sulfate or zinc-chelating dipeptide (beta-alanyl-L-histidinato zinc; AHZ) in the concentration range of 10(-7) to 10(-5) M. The inhibitory effect was seen at the earlier stage of osteoclast-like MNC formation. However, zinc compounds (10(-6) M) did not have an effect on PTH (10(-8) M)-induced osteoclast-like cell formation in the presence of EGTA (5 x 10(-4) M), dibucaine (10(-5) M) or staurosporine (10(-9) M). Moreover, when osteoclasts isolated from rat femoral-diaphyseal tissues were cultured for 24 h in the presence of zinc compounds (10(-7) to 10(-5) M), the compounds did not have an effect on cell numbers or lysosomal enzymes activity (acid phosphatase and beta-glucuronidase) in the cells. The present study clearly demonstrates that zinc compounds inhibit osteoclast-like cell formation at the earlier stage with differentiation of marrow cells.
Mol Cell Biochem 1996 May 24
PMID:Zinc compounds inhibit osteoclast-like cell formation at the earlier stage of rat marrow culture but not osteoclast function. 881 79

The technique of reverse transcription-PCR for mRNA phenotyping was applied to total RNA isolated from the two compartments of cancellous bone, namely trabecular bone and hematopoitic tissue or marrow. The pattern of gene expression for ten different growth factor ligands and five growth factor receptors was examined in total RNA isolated from the two compartments of cancellous bone of the female rat distal femur. Our results show that transcripts encoding IGF-I, IGF-II, transforming growth factor-beta 1 (TGF-beta 1), TGF-alpha, basic fibroblast growth factor, platelet-derived growth factor A and osteocalcin are detectable in samples from both trabeculae and marrow. Expression of epidermal growth factor (EGF) was confined to samples from trabeculae while nerve growth factor expression was only detected in marrow. Transcipts encoding insulin were not detected in any of the bone-derived samples in this study. Samples from cancellous bone trabeculae and marrow both showed evidence of expression of the genes encoding receptors for IGF-I, parathyroid hormone (PTH)/PTH-related protein and insulin. Neither compartment of cancellous bone contained transcripts encoding the receptor for IGF-II. Transcripts encoding the EGF receptor were detected in samples from cancellous bone marrow and not trabeculae as has been previously reported. These patterns of growth factor ligand and receptor gene expression suggest that it is likely that both autocrine and paracrine regulatory circuits are established in cancellous bone. This study also demonstrated the feasibility of assessing the expression of multiple genes from the small samples of total RNA obtained from separated tissues of cancellous bone. This is the first time that growth factor gene expression has been examined in separated trabeculae and marrow from cancellous bone and this approach will allow a more detailed analysis of molecular events in cancellous bone as opposed to whole bone or extracts of isolated and cultured bone cells.
J Mol Endocrinol 1996 Aug
PMID:Expression of growth factor ligand and receptor genes in rat cancellous bone trabeculae and marrow. 886 86

Secretion of parathyroid hormone-related protein (PTHrP) by sheep fetal parathyroid glands is reported to be an important factor in the maintenance of a placental calcium pump. The aim of the present study was to determine whether the developing rat parathyroid glands express PTHrP or parathyroid hormone (PTH), or both. Hybridisation histochemistry was used to detect transcription of PTHrP and PTH in serial paraffin sections through the 12.5- and 13.5-day rat embryo parathyroid anlage, as well as in sections through the 17.5-day embryonic and adult parathyroid glands. Results show strong expression of PTH in the 13.5-day embryonic parathyroid anlage, as well as in the parathyroid gland of the 17.5-day embryo and adult. Transcription of the PTHrP gene was not detected. The more sensitive technique of reverse transcription PCR was then performed. The pharyngeal region of 11.5-, 12.5- and 13.5-day rat embryos was dissected out and, at each stage, RNA was extracted from these tissues, as well as pooled tissues from the rest of the embryo. RNA that had been extracted from adult thyroid/parathyroid tissue was also tested. After reverse transcription, the resulting cDNAs were amplified by PCR (50 cycles) using specific PTH and PTHrP primers. The results show an abundance of PTH mRNA, specific to the pharyngeal region of the 13.5-day embryo, as well as to adult thyroid/parathyroid tissue. PTHrP expression was detected at very low levels in both parathyroid and extraparathyroid tissues. The presence of immunoreactive PTHrP and immunoreactive PTH in the pharyngeal region and rest of the body of 12.5- and 13.5-day rat embryos was assessed by specific RIAs. Whilst immunoreactive PTHrP was not detected in any of the tissues assayed, immunoreactive PTH was detected only in the pharyngeal region of the 13.5-day embryo. This confirms the results obtained from the gene expression studies. We conclude then that, in the developing rat embryo, PTH rather than PTHrP is more likely to play a role in calcium regulation. This is in contrast with the reported situation in the sheep, and suggests that fundamental species differences in fetal calcium regulation exist in mammals.
J Mol Endocrinol 1996 Oct
PMID:The expression of parathyroid hormone and parathyroid hormone-related protein in developing rat parathyroid glands. 893 90


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