Characterization of Cd‐induced molecular events prior to cellular damage in primary rat hepatocytes in culture: Activation of the stress activated signal protein JNK and transcription factor AP‐1

Hsiao, Chin Ju J; Stapleton, Susan R.

doi:10.1002/jbt.20018

Cited by 31 publications

(14 citation statements)

References 45 publications

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“…Alternatively, mitochondria represent a significant site of ROS formation by non-redox or poor redox cycling transition metals (Cd 2+ , Hg 2+ , As 3+ ) in rat hepatocytes (Pourahmad et al 2003), and Cd can have dual effects on respiratory chain activity and permeability transition (Belyaeva et al 2001). Cadmium, through the generation of ROS and prior to significant cellular damage, activates the stress-related signal protein c-Jun N-terminal kinase (JNK), increases c-jun expression, and promotes the binding of the transcription factor of activator protein-1 (AP-1) to DNA in primary cultures of rat hepatocytes (Hsiao & Stapleton 2004).…”

Section: Discussionmentioning

confidence: 99%

Kinetics of the early subcellular distribution of cadmium in rat hepatocytes

2005

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The kinetics of the early subcellular distribution of cadmium (Cd) was characterized in primary cultures of rat hepatocytes exposed to 10, 50 and 100 microM Cd in a serum-free WME medium for 10, 30 or 60 min. Our results demonstrate a time- and concentration-dependent increase in Cd content with the highest metal concentration measured in the cytosol, whereas the lowest was observed in the mitochondria. With the exception of early localization in the plasma membrane, Cd concentrations in fractions were characterized by the following decreasing order of magnitude: cytosol > low density molecules approximately nuclei > lysosomes approximately mitochondria. We also found evidence for: (i) a two-step process for Cd distribution in the nuclei and mitochondria; and (ii) a time-dependent 'slow' process of transfer from the plasma membrane to the cytosol. Saturation in Cd uptake was observed at 50 microM in most cell fractions at 10 and 30 min, except for the plasma membrane. The lack of apparent saturation for Cd accumulation at 60 min was not related to an increase in metallothionein synthesis. Altogether, our data provide insights into the dynamics of transfer between intracellular compartments, and allow a better identification of the organelles that are the most subjected to Cd toxicity for early exposure conditions.

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Section: Discussionmentioning

confidence: 99%

Kinetics of the early subcellular distribution of cadmium in rat hepatocytes

2005

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“…As a consequence of the breakdown of intracellular structures, calcium would be released from membrane-bound intracellular stores. Cadmium-induced oxidative stress and lipid peroxidation occur within minutes of exposure to toxic concentrations of metal and prior to any measurable cytotoxicity [49], [50], [51]. Metal-induced damage could activate multiple processes.…”

Section: Discussionmentioning

confidence: 99%

Cadmium Induces Transcription Independently of Intracellular Calcium Mobilization

2011

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BackgroundExposure to cadmium is associated with human pathologies and altered gene expression. The molecular mechanisms by which cadmium affects transcription remain unclear. It has been proposed that cadmium activates transcription by altering intracellular calcium concentration ([Ca2+]i) and disrupting calcium-mediated intracellular signaling processes. This hypothesis is based on several studies that may be technically problematic; including the use of BAPTA chelators, BAPTA-based fluorescent sensors, and cytotoxic concentrations of metal.Methodology/Principal FindingIn the present report, the effects of cadmium on [Ca2+]i under non-cytotoxic and cytotoxic conditions was monitored using the protein-based calcium sensor yellow cameleon (YC3.60), which was stably expressed in HEK293 cells. In HEK293 constitutively expressing YC3.60, this calcium sensor was found to be insensitive to cadmium. Exposing HEK293::YC3.60 cells to non-cytotoxic cadmium concentrations was sufficient to induce transcription of cadmium-responsive genes but did not affect [Ca2+]i mobilization or increase steady-state mRNA levels of calcium-responsive genes. In contrast, exposure to cytotoxic concentrations of cadmium significantly reduced intracellular calcium stores and altered calcium-responsive gene expression.Conclusions/SignificanceThese data indicate that at low levels, cadmium induces transcription independently of intracellular calcium mobilization. The results also support a model whereby cytotoxic levels of cadmium activate calcium-responsive transcription as a general response to metal-induced intracellular damage and not via a specific mechanism. Thus, the modulation of intracellular calcium may not be a primary mechanism by which cadmium regulates transcription.

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“…Overall changes at genomic DNA level in relation to Cd-exposure indicate that abiotic environmental factors, including heavy metals could have influential effects on appearance of new individual characteristics in plants. By previous researches it was demonstrated that Cd toxicity could cause various damages at DNA level, including base modifications and oxidations, single and double strand breaks, DNA-protein cross links, abasic sites, bulky adducts and DNA lesions such as 8-hydroxyguanine in organisms (Bisova et al, 1993;Hsiao and Stapleton, 2004). The occurrence of these various DNA mutations and lesions could also generate the substantial structural changes in genetic material thereby affecting the PCR kinetics (Bowditch et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Detection of physiological and genotoxic damages reflecting toxicity in Kalanchoe clones

Demir¹,

Tombuloğlu²,

Sakcali³

et al. 2016

Global NEST Journal

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In order to make assessments in understanding of physiological and genotoxic effects of imposing cadmium (Cd) on photosynthetic pigment contents along with the changes occurring in genetic material of Kalanchoe plants were used in relation to various Cd-treatments. Young plantlets were originated from a single host plant as clones, and developed in vitro. Developed clones were grown in standard pots with daily watering of Hoagland solution (20 ml) containing different concentrations of cadmium chloride for two months. Cd concentrations of the collected samples were measured by employing ICP-OES and RAPD-PCR technique was applied for detecting the genotoxic effects of Cd. After two month of experimental period, the comparisons between unexposed and exposed Kalanchoe clone groups revealed reductions in photosynthetic pigment contents, especially at the highest level of Cd exposure and a genomic instability when application of Cd concentration increases. RAPD-PCR analyses demonstrated the distinguishable banding pattern in number and band intensities between Cd-treated and control groups. In addition, progressive Cd accumulations in leaves, stems and roots of plant samples were observed when the application of exposure level increased.

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Characterization of Cd‐induced molecular events prior to cellular damage in primary rat hepatocytes in culture: Activation of the stress activated signal protein JNK and transcription factor AP‐1

Cited by 31 publications

References 45 publications

Kinetics of the early subcellular distribution of cadmium in rat hepatocytes

Kinetics of the early subcellular distribution of cadmium in rat hepatocytes

Cadmium Induces Transcription Independently of Intracellular Calcium Mobilization

Detection of physiological and genotoxic damages reflecting toxicity in Kalanchoe clones

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