Induction of cytoprotective autophagy in PC-12 cells by cadmium

Wang, Qiwen; Zhu, Jiaqiao; Zhang, Kangbao; Jiang, Chenyang; Wang, Yi; Yuan, Yan; Bian, Jianchun; Gu, Jianhong; Liu, Zongping

doi:10.1016/j.bbrc.2013.07.050

Cited by 62 publications

(37 citation statements)

References 35 publications

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“…So the function of autophagy in Cd-exposed cells can differ. Wang reported that cytoprotective autophagy could be induced by 20 μmol/L Cd at 4 h in neural cells [42]. In this study, we used biochemical assays to confirm that autophagy was activated during the process of Cd-induced cortical neuron injury, and we found that autophagy played a cytoprotective role during cadmium-induced oxidative damage in primary neurons.…”

Section: Discussionsupporting

confidence: 50%

Autophagy Plays a Cytoprotective Role During Cadmium-Induced Oxidative Damage in Primary Neuronal Cultures

Wang

Song

et al. 2015

Biol Trace Elem Res

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Cadmium (Cd) induces significant oxidative damage in cells. Recently, it was reported that autophagy could be induced by Cd in neurons. However, little is known about the role of reactive oxygen species (ROS) during Cd-induced autophagy. In our study, we examined the cross-talk between ROS and autophagy by using N-acetyl cysteine (NAC, an antioxidant) and chloroquine (CQ, a pharmacological inhibitor of autophagy) in a primary rat neuronal cell cultures. We observed accumulation of acidic vesicular organelles and the increased expression of endogenous protein light chain 3 (LC3) in Cd-treated neurons, revealing that Cd induced a high level of autophagy. Moreover, increased levels of ROS were observed in neurons treated with Cd, showing that ROS accumulation was closely associated with neuron's exposure to Cd. Furthermore, we found that autophagy was inhibited by using CQ and/or NAC with further aggravation of mitochondrial damage, lactate dehydrogenase (LDH) leakage and hypoploid apoptotic cell number in Cd-treated neurons. These results proved that autophagy has a cytoprotective role during Cd-induced toxicity in neurons, and it can prevent the oxidative damage. These findings may enable the development of novel therapeutic strategies for neurological diseases.

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Section: Discussionsupporting

confidence: 50%

Autophagy Plays a Cytoprotective Role During Cadmium-Induced Oxidative Damage in Primary Neuronal Cultures

Wang

Song

et al. 2015

Biol Trace Elem Res

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“…Therefore, measuring the level of LC3 II alone does not determine whether autophagy is induced or inhibited. Wang et al [27] showed that treatments of PC-12 cells with autophagy inhibitor chloroquine and autophagy inducer rapamycin can both increase LC3 II levels. The p62 protein, also called poly-ubiquitin binding protein sequestosome 1, is another marker of macroautophagy.…”

Section: Discussionmentioning

confidence: 99%

Chloroquine Enhances the Radiosensitivity of Bladder Cancer Cells by Inhibiting Autophagy and Activating Apoptosis

Wang

Tang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Chloroquine was formerly used as an anti-malarial agent drug but has now been proven to be useful for various diseases. This study aimed to investigate the radiosensitizing effect of chloroquine in bladder cancer, with an emphasis on autophagy inhibition and apoptosis induction. Methods: Bladder cancer cell lines were irradiated with or without chloroquine. Cell proliferation was determined by a Cell Counting Kit 8 assay. The radiosensitization effect of chloroquine was evaluated by clonogenic survival and progression of xenograft tumors. Cell apoptosis was detected by flow cytometry and western blot. Radiation-induced DNA double strand break was measured by the staining of γ-H2AX. In addition, autophagy was detected by western blot, immunofluorescence staining, and electron microscopy. Results: The treatment with chloroquine alone inhibited the proliferation of bladder cancer cells in a dose-dependent manner. Low cytotoxic concentrations of chloroquine enhanced the radiation sensitivity of bladder cancer cells with a sensitization enhancement ratio of 1.53 and 1.40. Chloroquine also obviously weakened the repair of radiation-induced DNA damage. A combination of radiation and chloroquine enhanced the apoptosis rate of EJ and T24 cells and down-regulated the expression of Bcl-2 while up-regulating the expression of caspase-3. Additionally, the relevant markers of autophagy were obviously increased in the combined group, meaning that chloroquine inhibited autophagy induced by irradiation. Furthermore, subcutaneous xenograft tumors displayed that the combination of radiation and chloroquine could impede tumorigenesis in vivo. Conclusion: In summary, these results provided support that by inhibiting autophagy and activating apoptosis, chloroquine might be a potentially promising radiosensitizer in the radiation therapy of bladder cancer.

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“…Many studies report that low-level cadmium exposure can cause cell autophagy in several types of cells such as PC12 cells, MES-13 mesangial cells, skin epidermal cells, and vascular endothelial cells [27,[34][35][36]. Low-level cadmium inhibits apoptosis by serum and basic fibroblast growth factor (bFGF) deprivation and promotes autophagy [35].…”

Section: Mechanisms Of Ca 2+ Homeostasis-mediated Cell Autophagy Indumentioning

confidence: 99%

Calcium Homeostasis Disruption - a Bridge Connecting Cadmium-Induced Apoptosis, Autophagy and Tumorigenesis

et al. 2015

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Calcium and cadmium are divalent metals and have similar chemical properties. Both can enter cells through, albeit different, channels, or through protein-dependent permeation. However, cadmium disturbs the calcium homeostasis by inhibiting calcium channels and/or related proteins. Cadmium can also alter membrane phospholipid concentrations, and so induce a calcium homeostasis disorder. The altered calcium homeostasis induced by cadmium results in cell apoptosis, autophagy or tumorigenesis. In this review, calcium homeostasis disruption is summarized as a bridge connecting cadmium-induced apoptosis, autophagy, and tumorigenesis.

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Induction of cytoprotective autophagy in PC-12 cells by cadmium

Cited by 62 publications

References 35 publications

Autophagy Plays a Cytoprotective Role During Cadmium-Induced Oxidative Damage in Primary Neuronal Cultures

Autophagy Plays a Cytoprotective Role During Cadmium-Induced Oxidative Damage in Primary Neuronal Cultures

Chloroquine Enhances the Radiosensitivity of Bladder Cancer Cells by Inhibiting Autophagy and Activating Apoptosis

Calcium Homeostasis Disruption - a Bridge Connecting Cadmium-Induced Apoptosis, Autophagy and Tumorigenesis

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