Maitotoxin, a calcium channel activator, inhibits cell cycle progression through the G1/S and G2/M transitions and prevents CDC2 kinase activation in GH4C1 cells

Dolah, Frances M. Van; Ramsdell, John S.

doi:10.1002/(sici)1097-4652(199601)166:1<49::aid-jcp6>3.0.co;2-g

Cited by 10 publications

(8 citation statements)

References 40 publications

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“…Reports in the literature indicate that the expression of VACCs is related to cell cycle progression. Smooth muscle cells, (26) GH4 pituitary cells, (27) and fibroblasts (28) have been shown to require L type currents for the transition through G1/S and/or G2/M. In osteoblastic cells, it has been difficult to correlate observed cytosolic calcium changes due to PTH stimulation and the position of the tested cell in the cell cycle (29,30) .…”

Section: Discussionmentioning

confidence: 99%

Molecular Characterization of the α1 Subunit of the L Type Voltage Calcium Channel Expressed in Rat Calvarial Osteoblasts

Loza

Carpio

Bradford

et al. 1999

Journal of Bone and Mineral Research

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Voltage-activated calcium channels (VACCs) regulate extracellular calcium influx in many cells. VACCs are composed of five subunits. The ␣ 1 subunit is considered the most important in regulating channel function. Three isoforms of this subunit have been described: skeletal, cardiac, and neuroendocrine. It was the purpose of the present study to determine the molecular identity of the ␣ 1 subunit of the VACCs in rat calvarial osteoblasts and to study the nature of the regulation of these channels as a function of cellular growth. We also attempted to identify which isoform of the ␣ 1 subunit of the VACCs mediates the effects of epidermal growth factor (EGF) on osteoblastic cell proliferation. Reverse transcription-polymerase chain reaction was used to detect the isoforms of the VACCs that are expressed in osteoblastic cells. These analyses showed that the proliferative state of the cell and the time in culture influence RNA expression. The only ␣ 1 subunit detected in osteoblasts corresponds to the cardiac isoform. In additional experiments, the effects of EGF on cytosolic calcium and osteoblast proliferation were determined. For these experiments, the synthesis of the different isoforms of the VACCs was selectively blocked by antisense oligonucleotides prior to EGF stimulation. These studies showed that the cardiac isoform mediates the effects of EGF on cytosolic calcium and cellular proliferation in rat calvarial osteoblasts. (J Bone Miner Res 1999;14:386-395)

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Section: Discussionmentioning

confidence: 99%

Molecular Characterization of the α1 Subunit of the L Type Voltage Calcium Channel Expressed in Rat Calvarial Osteoblasts

Loza

Carpio

Bradford

et al. 1999

Journal of Bone and Mineral Research

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“…12), which is consistent with the ability of deferoxamine to prevent 2-Br-6-(GSyl)HQ-mediated DNA damage (10) and cytotoxicity (9,10). Calcium also plays an important role in controlling cell proliferation and regulates progression through several cell cycle checkpoints, including the G 1 /S phase transition, the G 2 /M phase transition, and exit from mitosis (61). Calcium is also required for p34 cdc2 histone H1 kinase activity (62).…”

Section: The Role Of Iron Hydrogen Peroxide and Calcium In Quinone-mentioning

confidence: 99%

The Response of Renal Tubular Epithelial Cells to Physiologically and Chemically Induced Growth Arrest

Jeong¹,

Huang

Lau

et al. 1997

Journal of Biological Chemistry

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Cells respond to a variety of stresses by activating the transcription of a battery of "acute phase" or "stress response" genes. The nature of this response is tailored to the nature of the stress. The extent to which physiologically and pathophysiologically induced growth arrest share common genomic responses is unclear. We therefore compared the effects of a physiologically induced (serum and nutrient depletion) and a chemically induced (2-Br-bis-(GSyl)HQ and 2-Br-6-(GSyl)HQ) stress in renal tubular epithelial cells (LLC-PK 1 ). The response to physiological stress, induced by serum depletion, involves growth arrest characterized by an inhibition of DNA synthesis that occurs in the absence of a decrease in histone mRNA or an increase in gadd153 mRNA, one of the growth arrest and DNA damage inducible genes. In contrast, the chemical-induced stress involves growth arrest accompanied by a decrease in histone mRNA, particularly core histone H2B and H2A mRNA, and the induction of gadd153. Chemical-induced changes in histone mRNA inversely correlate to changes in the expression of a stress gene, hsp70, whose expression is dependent upon the maintenance of appropriate nucleosomal structure.Cells respond to a variety of stresses by activating the transcription of a battery of "acute phase" or "stress response" genes (1, 2). The nature of this response is tailored to the nature of the stress. For example, serum-and nutrient-deprived cells usually enter a quiescent state (G 0 ) that requires both the up-regulation and down-regulation of genes involved in growth control. In contrast, the initial response to DNA-damaging agents includes arrest of cell cycle progression, presumably to facilitate the transcription of a battery of genes involved in the DNA repair process (3) prior to DNA replication (G 1 arrest) and cell division (G 2 arrest). The extent to which physiologically and pathophysiologically induced growth arrest share common genomic responses is unclear and is the focus of the present studies.The conjugation of ortho-, or para-quinones with GSH results in the formation of conjugates that frequently exhibit more potent toxicological activity than the parent quinone (4). GSH conjugates of polyphenolics are also formed as metabolites of a variety of "non-genotoxic" carcinogens (5-7). As a model of quinone-thioether-mediated toxicity we have been investigating the cellular and molecular responses to 2-Br-bis-(glutathion-S-yl)hydroquinone (2-Br-bis-(GSyl)HQ) 1 and 2-Br-6-(glutathion-S-yl)hydroquinone (2-Br-6-(GSyl)HQ). 2-Br-bis-(GSyl)HQ (30 mol/kg) causes margination of heterochromatin and loss of chromatin staining when administered to male Fischer 344 rats (8), and in renal tubular epithelial cells (LLC-PK 1 ) it causes the formation of single strand breaks in DNA (9), rapid inhibition of DNA synthesis (10), and the induction of the growth arrest and DNA damage-inducible gene, gadd153 (10). Quinone-thioethers therefore provide a useful model with which to investigate chemically induced growth arrest and the consequ...

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“…Among marine toxins, maitotoxin ( 3 ) (see Chart ) is one of the most complex and lethal nonprotenaceous toxins known. This compound is a calcium channel activator which inhibits cell cycle progression through the G1/S and G2/M transitions and prevents CDC2 kinase activation in GH4Cl Cells . It also stimulates phosphoinositide breakdown in smooth muscle cells, NCB-20 cells, and PC12 cells through a nifedipine-insensitive mechanism .…”

Section: Database Contentmentioning

confidence: 99%

A Marine Natural Product Database

Lei

Zhou

2002

J. Chem. Inf. Comput. Sci.

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Maitotoxin, a calcium channel activator, inhibits cell cycle progression through the G1/S and G2/M transitions and prevents CDC2 kinase activation in GH4C1 cells

Cited by 10 publications

References 40 publications

Molecular Characterization of the α1 Subunit of the L Type Voltage Calcium Channel Expressed in Rat Calvarial Osteoblasts

Molecular Characterization of the α1 Subunit of the L Type Voltage Calcium Channel Expressed in Rat Calvarial Osteoblasts

The Response of Renal Tubular Epithelial Cells to Physiologically and Chemically Induced Growth Arrest

A Marine Natural Product Database

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