Comparative Studies of Chromaffin Cell Proliferation in the Adrenal Medulla of Rats and Mice

TISCHLER, ARTHUR S.; POWERS, JAMES F.; SHAHSAVARI, MEHZAD; ZIAR, JEFFREY; TSOKAS, PANAYIOTIS; DOWNING, JOHN; MCCLAIN, R. MICHAEL

doi:10.1093/toxsci/35.2.216

Cited by 10 publications

(14 citation statements)

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“…Mouse Chromaffin Cells; Isolation, Cell Culture, and Transient Transfection-Chromaffin cells were isolated using a modified Tischler method (15). Briefly, adrenal glands were dissected from 4 -10-week-old outbred Swiss Webster mice and placed into Ca 2ϩ -and Mg 2ϩ -free Locke's buffer that contained 154 mM NaCl, 2.6 mM KCl, 2.2 mM K 2 HPO 4 , 0.95 mM KH 2 PO 4 , 10 mM glucose, 10 mM HEPES (pH 7.2), supplemented with penicillin (200 g ml Ϫ1 )/streptomycin (50 g ml Ϫ1 ) at room temperature.…”

Section: Methodsmentioning

confidence: 99%

TRPC4 Can Be Activated by G-protein-coupled Receptors and Provides Sufficient Ca2+ to Trigger Exocytosis in Neuroendocrine Cells

Obukhov

Nowycky

2002

Journal of Biological Chemistry

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Transient receptor potential (TRP) channels form a large family of plasma membrane cation channels. Mammalian members of the "short" TRP family (TRP channel (TRPC) 1-7 are Ca 2؉ -permeant, non-selective cation channels that are widely expressed in various cell types, including neurons. TRPC activity is linked through unknown mechanisms to G-protein-coupled receptors or receptor tyrosine kinases that activate phospholipase C. entry. Since the cloning of the original trp gene (3), the "TRP" family of proteins has expanded rapidly. Recently, TRPs were subdivided into three groups, short, long, and Osm (4). Mammalian "short" TRP channels (TRPCs) 1 form a seven-member group of second messenger-operated, non-selective Ca 2ϩ -permeable cation channels (TRPC1-7) that can be activated by G-protein-coupled receptors or tyrosine receptor kinases. Phospholipase C plays a key role in stimulation of TRPC activity, although the specific mechanism of channel activation is unclear (5). Several activation mechanisms have been proposed, including stimulation by store depletion, direct coupling with IP 3 receptor/ryanodine receptors, and activation by second messengers such as diacylglycerol (6 -10).TRPCs are widely expressed in mammalian tissues, and the mRNAs of some isoforms such as TRPC4 and TRPC5 are expressed predominantly in brain (11-13). To date, almost all studies of TRPC isoforms have been performed in non-excitable expression systems such as HEK293 cells, Chinese hamster ovary cells, and oocytes (5). There is no universal agreement on the ion selectivity and kinetic properties of individual TRPCs. At least part of the controversy arises because TRPC isoforms can exhibit different characteristics in different cellular environments (14).Neurotransmitter release in neurons and neuroendocrine cells is triggered by a rise in [Ca 2ϩ ]. Voltage-gated Ca 2ϩ channels (VGCC) provide highly localized, rapid [Ca 2ϩ ] elevations. Additional Ca 2ϩ entry pathways, however, may trigger or modulate exocytosis. For example, numerous metabotropic presynaptic receptors can modulate synaptic release via second messenger systems. G-protein-coupled receptors that activate phospholipase C␤ cause release of Ca 2ϩ from intracellular stores and may activate additional cationic conductances such as store-operated or other cation channels. To determine whether TRPCs can respond to G-protein-coupled receptor signaling and mediate exocytosis in neuronal cells, we transiently expressed TRPC4 in mouse adrenal chromaffin cells, which are developmentally related to sympathetic neurons.We found that stimulation of TRPC4 via the G q/11 -linked histamine H 1 receptor induced exocytosis in chromaffin cells co-transfected with TRPC4 and H 1 -R. Thapsigargin and IP 3 did not stimulate TRPC4 in the cells, suggesting that activation is not store-operated. Because TRPC4 is abundant in hippocampal pyramidal neurons and cortical neurons (11), we propose that activation of by agonists of metabotropic receptors may regulate secretory responses in neurons. EXPERIM...

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Section: Methodsmentioning

confidence: 99%

TRPC4 Can Be Activated by G-protein-coupled Receptors and Provides Sufficient Ca2+ to Trigger Exocytosis in Neuroendocrine Cells

Obukhov

Nowycky

2002

Journal of Biological Chemistry

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“…The mean tumor size increases progressively with age, as does the frequency of bilateral and multicentric occurrence. Both spontaneous and xenobiotic induced pheochrom ocytom as are less com mon in the mouse (22).…”

Section: Pheochromocytomasmentioning

confidence: 97%

Adrenal Gland: Structure, Function, and Mechanisms of Toxicity

et al. 2001

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The adrenal gland is one of the most comm on endocrine organs affected by chemically induced lesions. In the adrenal cortex, lesions are more frequent in the zona fasciculata and reticularis than in the zona glomerulosa. The adrenal cortex produces steroid hormones with a 17-carbon nucleus following a series of hydroxyla tion reactions that occur in the m itochondria and endoplasm ic reticulum. Toxic agents for the adrenal cortex include short-chain aliphatic compound s, lipidosis inducers , amphiphilic compounds , natural and synthetic steroids, and chemicals that affect hydroxyla tion. Morphologic evaluation of cortical lesions provides insight into the sites of inhibition of steroidogenesis. The adrenal cortex response to injury is varied. Degeneratio n (vacuolar and granular), necrosis, and hem orrhage are common ndings of acute injury. In contrast, chronic reparative processes are typically atrophy, brosis, and nodular hyperplasia. Chem ically induced proliferative lesions are uncom m on in the adrena l cortex. The adrenal medulla contains chrom af n cells (that produce epinephrine, norepineph rine, chromogranin, and neuropeptides) and ganglion cells. Proliferative lesions of the medulla are common in the rat and include diffuse or nodular hyperplasia and benign and malignant pheochrom ocytoma. Mechanism s of chromaf n cell proliferation in rats include excess growth hormone or prolactin, stimulation of cholinergic nerves, and diet-induced hypercalcem ia. There often are species speci city and age dependenc e in the developme nt of chemically induced adrenal lesions that should be considered when interpreting toxicity data.

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“…The level of c-myc gene expression was also reduced in ArKO mice, by approximately 30% compared with that in WT adrenals (P < 0.05). To determine if estrogen reverses the reduced gene expressions of TERT and c-myc, a hormone replacement therapy was conducted in these WT and ArKO animals, followed by gene expres- [26,27], and we assumed that the poor BrdU uptake was due to the short delivery time of BrdU (2 h prior to tissue collection) compared with other adrenal gland studies that typically used a mini-osmotic pump delivery system over a 7-day period [26,28]. To overcome this problem, adrenal gland sections were stained with a specific antibody for the Ki67 protein that is expressed during all stages of the cell cycle, but repressed in G 0 [29].…”

Section: Reduced Gene Expression Of the Tert In Estrogen-deficient Micementioning

confidence: 99%

Estrogen deficiency leads to telomerase inhibition, telomere shortening and reduced cell proliferation in the adrenal gland of mice

Bayne

Jones

et al. 2008

Cell Res

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Estrogen deficiency mediates aging, but the underlying mechanism remains to be fully determined. We report here that estrogen deficiency caused by targeted disruption of aromatase in mice results in significant inhibition of telomerase activity in the adrenal gland in vivo. Gene expression analysis showed that, in the absence of estrogen, telomerase reverse transcriptase (TERT) gene expression is reduced in association with compromised cell proliferation in the adrenal gland cortex and adrenal atrophy. Stem cells positive in c-kit are identified to populate in the parenchyma of adrenal cortex. Analysis of telomeres revealed that estrogen deficiency results in significantly shorter telomeres in the adrenal cortex than that in wild-type (WT) control mice. To further establish the causal effects of estrogen, we conducted an estrogen replacement therapy in these estrogen-deficient animals. Administration of estrogen for 3 weeks restores TERT gene expression, telomerase activity and cell proliferation in estrogen-deficient mice. Thus, our data show for the first time that estrogen deficiency causes inhibitions of TERT gene expression, telomerase activity, telomere maintenance, and cell proliferation in the adrenal gland of mice in vivo, suggesting that telomerase inhibition and telomere shortening may mediate cell proliferation arrest in the adrenal gland, thus contributing to estrogen deficiency-induced aging under physiological conditions.

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Comparative Studies of Chromaffin Cell Proliferation in the Adrenal Medulla of Rats and Mice

Cited by 10 publications

References 20 publications

TRPC4 Can Be Activated by G-protein-coupled Receptors and Provides Sufficient Ca2+ to Trigger Exocytosis in Neuroendocrine Cells

TRPC4 Can Be Activated by G-protein-coupled Receptors and Provides Sufficient Ca2+ to Trigger Exocytosis in Neuroendocrine Cells

Adrenal Gland: Structure, Function, and Mechanisms of Toxicity

Estrogen deficiency leads to telomerase inhibition, telomere shortening and reduced cell proliferation in the adrenal gland of mice

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