Regulation of parathyroid hormone gene expression and peptide secretion in human parathyroid cells

Liu J, Kahri AI, Teppo A-M, Voutilainen R. Regulation of parathyroid hormone gene expression and peptide secretion in human parathyroid cells. Eur J Endocrinol 1994;130:394–401. ISSN 0804–4643 In cell cultures prepared from human parathyroid adenomas, parathyroid hormone (PTH) mRNA expression decreased slowly. During short-term incubations (less than 24), a low calcium concentration (0.5 mmol/l) and protein kinase C activator TPA (12-O-tetradecanoyl phorbol 13-acetate) (160 nmol/l) increased PTH secretion (60%; p <0.05), while a high extracellular calcium concentration (2.5 mmol/l) reduced PTH secretion (60%; p<0.05), The TPA could block the inhibitory effect of a high calcium level on PTH peptide secretion. All these agents had no effect on PTH mRNA accumulation in short-term experiments. In long-term cultures (more than 24 h), a low calcium level increased and a high calcium level reduced both PTH mRNA (85 and 34%; p <0.05) and peptide secretion (140 and 80%; p <0.05), respectively. The TPA reduced PTH mRNA accumulation down to 30% (p<0.05) and PTH secretion down to 14% (p<0.05) in a time- and dose-dependent fashion. The TPA also reversed the stimulatory effect of hypocalcemia on PTH mRNA accumulation and peptide secretion. Protein kinase C inhibitors staurosporine (100 nmol/l) and H-7 (1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride) (50 μmol/l) had similar effects to TPA on PTH gene expression and peptide secretion in long-term cultures. The results support the hypothesis that extracellular calcium regulates PTH mRNA accumulation and PTH secretion via protein kinase C. Raimo Voutilainen, Department of Pathology, PO Box 21 (Haartmaninkatu 3), SF-00014 University of Helsinki, Finland

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Effect of phorbol myristate acetate on secretion of parathyroid hormone

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1988.254.1.e63 ◽

1988 ◽

Vol 254 (1) ◽

pp. E63-E70 ◽

Cited By ~ 1

Author(s):

J. J. Morrissey

Keyword(s):

Protein Kinase C ◽

Parathyroid Hormone ◽

Protein Kinase ◽

Membrane Fraction ◽

Hormone Secretion ◽

Myristate Acetate ◽

Kinase C ◽

Low Calcium ◽

Protein Kinase C Activity ◽

High Calcium

The influence of phorbol myristate acetate (PMA), an activator of protein kinase c, on the secretion of parathyroid hormone from collagenase-dispersed bovine parathyroid cells was tested. The cells were incubated at low (0.5 mM) or high (2.0 mM) concentrations of calcium in the medium, and the hormone secreted into the medium was measured by a radioimmunoassay that recognizes both intact and C-terminal fragments of hormone. At low calcium, the secretory rate averaged 32 +/- 3.8 ng.h-1.(10(5) cells)-1. The addition of 1.6 microM PMA did not affect secretion. At high calcium there was a significant suppression of secretion by 38% to 19.8 +/- 3 ng.h-1.(10(5) cells)-1. The addition of 1.6 microM PMA significantly stimulated hormone secretion to 35.8 +/- 8 ng.h-1.(10(5) cells)-1, a rate indistinguishable from low calcium. This stimulatory effect of PMA at high calcium was seen at PMA concentrations as low as 1.6 nM, did not occur with a biologically inactive 4 alpha-isomer of phorbol ester, and was independent of changes in cellular adenosine 3',5'-cyclic monophosphate levels. Examination of 32P-labeled phosphoproteins by two-dimensional gel electrophoresis revealed acidic proteins of approximately 20,000 and 100,000 Da that were phosphorylated at low and high calcium + 1.6 microM PMA but not at high calcium alone. The protein kinase c activity associated with the membrane fraction of parathyroid cells significantly decreased 40% when the cells were incubated at high vs. low calcium. The data suggest that calcium may regulate parathyroid hormone secretion through changes in protein kinase c activity of the membrane fraction of the cell and protein phosphorylation.

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Analysis of differential gene expression supports a role for amyloid precursor protein and a protein kinase C substrate (MARCKS) in long-term memory

European Journal of Neuroscience ◽

10.1046/j.1460-9568.2003.02539.x ◽

2003 ◽

Vol 17 (5) ◽

pp. 1073-1081 ◽

Cited By ~ 25

Author(s):

R. O. Solomonia ◽

K. Morgan ◽

A. Kotorashvili ◽

B. J. McCabe ◽

A. P. Jackson ◽

...

Keyword(s):

Gene Expression ◽

Protein Kinase C ◽

Protein Kinase ◽

Amyloid Precursor Protein ◽

Differential Gene Expression ◽

Long Term Memory ◽

Term Memory ◽

Kinase C ◽

Differential Gene

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Adrenomedullin gene expression and its different regulation in human adrenocortical and medullary tumors

Journal of Endocrinology ◽

10.1677/joe.0.1550483 ◽

1997 ◽

Vol 155 (3) ◽

pp. 483-490 ◽

Cited By ~ 22

Author(s):

J Liu ◽

AI Kahri ◽

P Heikkila ◽

R Voutilainen

Keyword(s):

Gene Expression ◽

Protein Kinase C ◽

Protein Kinase ◽

Adrenal Medulla ◽

Adrenal Glands ◽

Primary Cultures ◽

Mrna Accumulation ◽

Adrenal Cells ◽

Pheochromocytoma Cells ◽

Kinase C

Adrenomedullin (ADM) is a polypeptide originally discovered in a human pheochromocytoma and is also present in normal adrenal medulla. It has been proposed that ADM could be involved in the regulation of adrenal steroidogenesis via paracrine mechanisms. Our aim was to find out if ADM gene is expressed in adrenocortical tumors and how ADM gene expression is regulated in adrenal cells. ADM mRNA was detectable by Northern blotting in most normal and hyperplastic adrenals, adenomas and carcinomas. The average concentration of ADM mRNA in the hormonally active adrenocortical adenomas was about 80% and 7% of that in normal adrenal glands and separated adrenal medulla respectively. In adrenocortical carcinomas, the ADM mRNA concentration was very variable, but on average it was about six times greater than that in normal adrenal glands. In pheochromocytomas, ADM mRNA expression was about ten times greater than that in normal adrenals and three times greater than in separated adrenal medulla. In primary cultures of normal adrenal cells, a protein kinase C inhibitor, staurosporine, reduced ADM mRNA accumulation in a dose- and time-dependent fashion (P < 0.01), whereas it simultaneously increased the expression of human cholesterol side-chain cleavage enzyme (P450 scc) gene (a key gene in steroidogenesis). In cultured Cushing's adenoma cells, adrenocorticotropin, dibutyryl cAMP ((Bu)2cAMP) and staurosporine inhibited the accumulation of ADM mRNA by 40, 50 and 70% respectively (P < 0.05), whereas the protein kinase C activator, 12-O-tetradecanoyl phorbol 13-acetate (TPA), increased it by 50% (P < 0.05). In primary cultures of pheochromocytoma cells, treatment with (Bu)2cAMP for 1 and 3 days increased ADM mRNA accumulation two- to threefold (P < 0.05). Our results show that ADM mRNA is present not only in adrenal medulla and pheochromocytomas, but also in adrenocortical neoplasms. Both protein kinase A- and C-dependent mechanisms regulate ADM mRNA expression in adrenocortical and pheochromocytoma cells supporting the suggested role for ADM as an autocrine or paracrine (or both) regulator of adrenal function.

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Faculty Opinions recommendation of Protein kinase C delta phosphorylates ecdysone receptor B1 to promote gene expression and apoptosis under 20-hydroxyecdysone regulation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.728367419.793536652 ◽

2017 ◽

Author(s):

Kang Le

Keyword(s):

Gene Expression ◽

Protein Kinase C ◽

Protein Kinase ◽

Ecdysone Receptor ◽

Protein Kinase C Delta ◽

Kinase C

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Protein kinase C injection into hippocampal pyramidal cells elicits features of long term potentiation

Nature ◽

10.1038/328426a0 ◽

1987 ◽

Vol 328 (6129) ◽

pp. 426-429 ◽

Cited By ~ 251

Author(s):

G.-Y. Hu ◽

Ø. Hvalby ◽

S. I. Walaas ◽

K. A. Albert ◽

P. Skjeflo ◽

...

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Pyramidal Cells ◽

Long Term Potentiation ◽

Kinase C ◽

Term Potentiation ◽

Hippocampal Pyramidal Cells

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The role of PKMζ in the maintenance of long-term memory: a review

Reviews in the Neurosciences ◽

10.1515/revneuro-2020-0105 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Hamish Patel ◽

Reza Zamani

Keyword(s):

Protein Kinase C ◽

Protein Kinase ◽

Long Term Potentiation ◽

Global Memory ◽

Long Term Memory ◽

Compensatory Mechanism ◽

Term Memory ◽

Kinase C

Abstract Long-term memories are thought to be stored in neurones and synapses that undergo physical changes, such as long-term potentiation (LTP), and these changes can be maintained for long periods of time. A candidate enzyme for the maintenance of LTP is protein kinase M zeta (PKMζ), a constitutively active protein kinase C isoform that is elevated during LTP and long-term memory maintenance. This paper reviews the evidence and controversies surrounding the role of PKMζ in the maintenance of long-term memory. PKMζ maintains synaptic potentiation by preventing AMPA receptor endocytosis and promoting stabilisation of dendritic spine growth. Inhibition of PKMζ, with zeta-inhibitory peptide (ZIP), can reverse LTP and impair established long-term memories. However, a deficit of memory retrieval cannot be ruled out. Furthermore, ZIP, and in high enough doses the control peptide scrambled ZIP, was recently shown to be neurotoxic, which may explain some of the effects of ZIP on memory impairment. PKMζ knockout mice show normal learning and memory. However, this is likely due to compensation by protein-kinase C iota/lambda (PKCι/λ), which is normally responsible for induction of LTP. It is not clear how, or if, this compensatory mechanism is activated under normal conditions. Future research should utilise inducible PKMζ knockdown in adult rodents to investigate whether PKMζ maintains memory in specific parts of the brain, or if it represents a global memory maintenance molecule. These insights may inform future therapeutic targets for disorders of memory loss.

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