Dataset Information

Cadmium induces autophagy through ROS-dependent activation of the LKB1-AMPK signaling in skin epidermal cells.

ABSTRACT: Cadmium is a toxic heavy metal which is environmentally and occupationally relevant. The mechanisms underlying cadmium-induced autophagy are not yet completely understood. The present study shows that cadmium induces autophagy, as demonstrated by the increase of LC3-II formation and the GFP-LC3 puncta cells. The induction of autophagosomes was directly visualized by electron microscopy in cadmium-exposed skin epidermal cells. Blockage of LKB1 or AMPK by siRNA transfection suppressed cadmium-induced autophagy. Cadmium-induced autophagy was inhibited in dominant-negative AMPK-transfected cells, whereas it was accelerated in cells transfected with the constitutively active form of AMPK. mTOR signaling, a negative regulator of autophagy, was downregulated in cadmium-exposed cells. In addition, cadmium generated reactive oxygen species (ROS) at relatively low levels, and caused poly(ADP-ribose) polymerase-1 (PARP) activation and ATP depletion. Inhibition of PARP by pharmacological inhibitors or its siRNA transfection suppressed ATP reduction and autophagy in cadmium-exposed cells. Furthermore, cadmium-induced autophagy signaling was attenuated by either exogenous addition of catalase and superoxide dismutase, or by overexpression of these enzymes. Consequently, these results suggest that cadmium-mediated ROS generation causes PARP activation and energy depletion, and eventually induces autophagy through the activation of LKB1-AMPK signaling and the down-regulation of mTOR in skin epidermal cells.

SUBMITTER: Son YO

PROVIDER: S-EPMC3439510 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Cadmium induces autophagy through ROS-dependent activation of the LKB1-AMPK signaling in skin epidermal cells.

Son Young-Ok YO Wang Xin X Hitron John Andrew JA Zhang Zhuo Z Cheng Senping S Budhraja Amit A Ding Songze S Lee Jeong-Chae JC Shi Xianglin X

Toxicology and applied pharmacology 20110713 3

Cadmium is a toxic heavy metal which is environmentally and occupationally relevant. The mechanisms underlying cadmium-induced autophagy are not yet completely understood. The present study shows that cadmium induces autophagy, as demonstrated by the increase of LC3-II formation and the GFP-LC3 puncta cells. The induction of autophagosomes was directly visualized by electron microscopy in cadmium-exposed skin epidermal cells. Blockage of LKB1 or AMPK by siRNA transfection suppressed cadmium-indu ...[more]

PMID: 21767558

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Dataset Information

Cadmium induces autophagy through ROS-dependent activation of the LKB1-AMPK signaling in skin epidermal cells.

Publications

Cadmium induces autophagy through ROS-dependent activation of the LKB1-AMPK signaling in skin epidermal cells.

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