Gap Junctions and the Regulation of Cellular Functions of Stem Cells during Development and Differentiation

Trosko, James E.; Chang, Chia Cheng; Wilson, Melinda R.; Upham, Brad L.; Hayashi, Tomonori; Wade, Margaret

doi:10.1006/meth.1999.0941

Cited by 161 publications

(110 citation statements)

References 41 publications

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“…To determine whether the Cx47 mutants can form functional gap junctions, we scrape loaded cells (el-Fouly et al 1987;Trosko et al 2000). In this assay, a confluent monolayer of cells is injured with a scalpel blade in media that contains 0.1% Lucifer Yellow (LY; MW 443) or 2% neurobiotin (NB; MW 287).…”

Section: Cx47 Mutants Do Not Form Functional Channelsmentioning

confidence: 99%

Loss-of-function GJA12/Connexin47 mutations cause Pelizaeus–Merzbacher-like disease

Orthmann-Murphy

Enriquez

Abrams

et al. 2007

Molecular and Cellular Neuroscience

121

112

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Section: Cx47 Mutants Do Not Form Functional Channelsmentioning

confidence: 99%

Loss-of-function GJA12/Connexin47 mutations cause Pelizaeus–Merzbacher-like disease

Orthmann-Murphy

Enriquez

Abrams

et al. 2007

Molecular and Cellular Neuroscience

121

112

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“…Detailed methods were previously described. 39 PAHs (70 lM) were added to 2 ml of KBM plus 5 lM forskolin or 5 lM forskolin with the addition of 200 lM IBMX based on previous experiments. 40 PAHs and forskolin/IBMX were made up in 100% acetonitrile.…”

Section: Gap Junctional Intercellular Communicationmentioning

confidence: 99%

Cigarette smoke components inhibited intercellular communication and differentiation in human pancreatic ductal epithelial cells

Tai

Upham

Olson

et al. 2007

Intl Journal of Cancer

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Smoking is a well-documented risk factor for the development of pancreatic adenocarcinoma. Although the most abundant polycyclic aromatic hydrocarbons (PAHs) in cigarette smoke are methylated anthracenes and phenanthrenes, the epigenetic toxicity of these compounds has not been extensively studied. We previously showed that methylanthracenes, which possess a bay-like structure, affect epigenetic events such as an induced release of arachidonic acid, inhibition of gap junctional intercellular communication (GJIC) and induction of mitogen-activated protein kinases in a pluripotent rat liver epithelial stem cell line. Anthracenes with no bay-like structures were inactive. These biological effects are all molecular events associated with the promotional phase of cancer. A human immortalized, nontumorigenic pancreatic ductal epithelial cell line, H6c7, was examined to study the epigenetic toxicity of PAHs related to pancreatic cancer by using scrape-loading dye transfer, immunostaining, RT-PCR and telomerase assay methods. H6c7 cells were GJIC-incompetent and exhibited high telomerase activity when grown in growth factor and hormonesupplemented medium. In the presence of the cAMP elevating drugs (forskolin and IBMX) the cells became GJIC competent and expressed connexins. Telomerase activity was also decreased by cAMP elevating drug treatment. After induction of cAMP, 1-methylanthracene with bay-like structures inhibited GJIC, whereas the 2-methylanthracene lacking a bay-like structure had no effect on GJIC. Telomerase activity remained high in 1-methylanthracene treatment but not with 2-methylanthracene. These results indicate that a prominent component of cigarette smoke, namely methylanthracenes with distinct structural configurations, could be a potential etiological agent contributing to the epigenetic events of pancreatic cancer. ' 2007 Wiley-Liss, Inc.Key words: connexin 36; telomerase; PAH; gap junction Pancreatic cancer is the fourth most common cause of cancerrelated death in the United States. 1,2 Incidence in the developed world parallels the United States, and in undeveloped nations the incidence is lower, which could be due to underreporting. 3 There are no early screening tests and no universally-effective treatment options, making this disease one of the most fatal cancers known, with a 5-year survival rate of less than 5%. 1,3-5 A recent article even suggested no patients are actually ''cured'' of this disease. 6 Although several risk factors, such as diet, have been associated with pancreatic cancer, cigarette smoking is the only unequivocal risk factor that has been identified. 1,7-9 The incidence of pancreatic cancer is 50-90% higher among blacks in the United States than whites. This disparity has been linked primarily to cigarette smoking-and to a lesser extent diabetes-in men, 10 again indicating the significance of tobacco smoke in the incidence of pancreatic cancer.Although cigarette smoke has been identified as one etiological cause of pancreatic cancer, the underlying molecular mechanism ca...

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“…Regulation of tumor (Loewenstein and Rose, 1992;Yamasaki et al, 1995;Krutovskikh and Yamasaki, 1997;Li and Herlyn, 2000;Omori et al, 2001) and stem cell (Trosko et al, 2000;Burnside and Collas, 2002;Tazuke et al, 2002;Gilboa et al, 2003;Cai et al, 2004;Wong et al, 2004) …”

Section: Gap Junctional Signalingmentioning

confidence: 99%

Mathematical model of morphogen electrophoresis through gap junctions

Esser

Smith

Weaver

et al. 2006

Developmental Dynamics

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Gap junctional communication is important for embryonic morphogenesis. However, the factors regulating the spatial properties of small molecule signal flows through gap junctions remain poorly understood. Recent data on gap junctions, ion transporters, and serotonin during left-right patterning suggest a specific model: the net unidirectional transfer of small molecules through long-range gap junctional paths driven by an electrophoretic mechanism. However, this concept has only been discussed qualitatively, and it is not known whether such a mechanism can actually establish a gradient within physiological constraints. We review the existing functional data and develop a mathematical model of the flow of serotonin through the early Xenopus embryo under an electrophoretic force generated by ion pumps. Through computer simulation of this process using realistic parameters, we explored quantitatively the dynamics of morphogen movement through gap junctions, confirming the plausibility of the proposed electrophoretic mechanism, which generates a considerable gradient in the available time frame. The model made several testable predictions and revealed properties of robustness, cellular gradients of serotonin, and the dependence of the gradient on several developmental constants. This work quantitatively supports the plausibility of electrophoretic control of morphogen movement through gap junctions during early left-right patterning. This conceptual framework for modeling gap junctional signaling-an epigenetic patterning mechanism of wide relevance in biological regulation-suggests numerous experimental approaches in other patterning systems.

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Gap Junctions and the Regulation of Cellular Functions of Stem Cells during Development and Differentiation

Cited by 161 publications

References 41 publications

Loss-of-function GJA12/Connexin47 mutations cause Pelizaeus–Merzbacher-like disease

Loss-of-function GJA12/Connexin47 mutations cause Pelizaeus–Merzbacher-like disease

Cigarette smoke components inhibited intercellular communication and differentiation in human pancreatic ductal epithelial cells

Mathematical model of morphogen electrophoresis through gap junctions

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