The modulation of gap junctional communication by gossypol in various mammalian cell lines in vitro*1

Ye, Yi-Xin; Bombick, David W.; Hirst, Kendalyn; Zhang, Guixiang; Chang, Chia‐Cheng; Trosko, James E.; Akera, Tai

doi:10.1016/0272-0590(90)90306-5

Cited by 23 publications

(3 citation statements)

References 27 publications

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“…Several reports have postulated different mechanisms to explain the cytotoxic effects of GA, e.g. , inhibition of several enzymes (protein kinase C, lactate dehydrogenase, adenylate cyclase, acrosin) [25], disruption of cell-to-cell communication at the level of gap junctions [31] and damage to the cellular ultrastructure, with mitochondria being the main target [24]. …”

Section: Discussionmentioning

confidence: 99%

Gossypol acetic acid induces apoptosis in RAW264.7 cellsviaa caspase-dependent mitochondrial signaling pathway

Deng

Yuan

et al. 2013

J Vet Sci

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To investigate the effects of gossypol acetic acid (GA) on proliferation and apoptosis of the macrophage cell line RAW264.7 and further understand the possible underlying mechanism responsible for GA-induced cell apoptosis, RAW264.7 cells were treated with GA (25~35 µmol/L) for 24 h and the cytotoxicity was determined by MTT assay, while apoptotic cells were identified by TUNEL assay, acridine orange/ethidium bromide staining and flow cytometry. Moreover, mitochondrial membrane potential (ΔΨm) with Rhodamine 123 and reactive oxygen species (ROS) with DCFH-DA were analyzed by fluorescence spectrofluorometry. In addition, the expression of caspase-3 and caspase-9 was assessed by Western Blot assay. Finally, the GA-induced cell apoptosis was evaluated by flow cytometry in the present of caspase inhibitors Z-VAD-FMK and Ac-LEHD-FMK, respectively. GA significantly inhibited the proliferation of RAW264.7 cells in a dose-dependent manner, and caused obvious cell apoptosis and a loss of ΔΨm in RAW264.7 cells. Moreover, the ROS production in cells was elevated, and the levels of activated caspase-3 and caspase-9 were up-regulated in a dose-dependent manner. Notably, GA-induced cell apoptosis was markedly inhibited by caspase inhibitors. These results suggest that GA-induced RAW264.7 cell apoptosis may be mediated via a caspase-dependent mitochondrial signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Gossypol acetic acid induces apoptosis in RAW264.7 cellsviaa caspase-dependent mitochondrial signaling pathway

Deng

Yuan

et al. 2013

J Vet Sci

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“…Altered GJIC has also been implicated in teratogenesis (), reproductive dysfunction ( − ), alteration of muscle contractions in heart and uterus ( , ), and neuropathy (). Obviously, the interruption of GJIC disrupts the homeostasis of the organism leading to various chronic diseases, depending on the cell- and tissue-type where communication is altered.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Toxicity of a Mixture of Polycyclic Aromatic Hydrocarbons on Gap Junctional Intercellular Communication Before and After Biodegradation

Ghoshal

Weber

Rummel

et al. 1999

Environ. Sci. Technol.

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Polycyclic aromatic hydrocarbons (PAHs) are known carcinogens, but most research on their toxicity in the development of human-risk assessment models has focused on genotoxicity. Many nongenotoxic PAHs, however, have been shown to be epigenetically toxic by disrupting gap junctional intercellular communication (GJIC), an effect which has been affiliated with tumor promotion. We therefore used GJIC as an epigenetic biomarker to assess the toxic effect of a nonaqueous phase liquid (NAPL) mixture of PAHs commonly found in coal tar and creosote products. The NAPL mixture consisted of toluene, naphthalene, 1-methylnaphthalene, 2-ethylnaphthalene, acenaphthene, fluorene, phenanthrene, fluoranthene, and pyrene. This mixture reversibly inhibited GJIC at a maximal and noncytotoxic dose of 60 μM. Inhibition occurred within 5 min, indicating a post-translational modification of gap junction proteins. Biodegradation of globules of this mixture suspended in mineral media by a microorganism isolated from creosote-contaminated soils resulted in the removal of all but three heavy PAHs: acenaphthene, pyrene, and fluoranthene. A reconstituted mixture of these three compounds showed results on GJIC activity identical to the original mixture relative to dose-, rate-, and time-responses, indicating that the toxicity of the PAHs was additive. The results suggest that bioremediation techniques that leave residual components of such NAPL mixtures in contaminated media can quantitatively but not qualitatively reduce their epigenetic toxic risk. Nonetheless, such bioresistant residuals may be environmentally less mobile than the biodegraded components of the precursor NAPLs.

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“…Although, PFOA and PFDA are not metabolized, they have been found to inhibit GJIC in rat liver epithelial cells and human kidney epithelial cells at concentrations of 100 and 250 μM, respectively (). The inhibition of GJIC has been implicated in tumor promotion during carcinogenesis ( − ), teratogenesis (), and reproductive dysfunction ( − ).…”

Section: Fate and Effects Of Nonvolatile Fluorinated Organicsmentioning

confidence: 99%

Fluorinated Organics in the Biosphere

Key

Howell

Criddle

1997

Environ. Sci. Technol.

670

407

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The use of organofluorine compounds has increased throughout this century, and they are now ubiquitous environmental contaminants. Although generally viewed as recalcitrant because of their lack of chemical reactivity, many fluorinated organics are biologically active. Several questions surround their distribution, fate, and effects. Of particular interest is the fate of perfluoroalkyl substituents, such as the trifluoromethyl group. Most evidence to date suggest that such groups resist defluorination, yet they can confer significant biological activity. Certain volatile fluorinated compounds can be oxidized in the troposphere yielding nonvolatile compounds, such as trifluoroacetic acid. In addition, certain nonvolatile fluorinated compounds can be transformed in the biosphere to volatile compounds. Research is needed to assess the fate and effects of nonvolatile fluorinated organics, the fluorinated impurities present in commercial formulations, and the transformation products generated by biochemical processes and/or oxidation in the troposphere.

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The modulation of gap junctional communication by gossypol in various mammalian cell lines in vitro*1

Cited by 23 publications

References 27 publications

Gossypol acetic acid induces apoptosis in RAW264.7 cellsviaa caspase-dependent mitochondrial signaling pathway

Gossypol acetic acid induces apoptosis in RAW264.7 cellsviaa caspase-dependent mitochondrial signaling pathway

Epigenetic Toxicity of a Mixture of Polycyclic Aromatic Hydrocarbons on Gap Junctional Intercellular Communication Before and After Biodegradation

Fluorinated Organics in the Biosphere

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