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Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine
Jun, 2024;37 (3): 609-629.

Cadmium toxicity and autophagy: a review.

Yueting Shao, Liting Zheng, Yiguo Jiang
Author Information
  1. Yueting Shao: Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, 511436, China.
  2. Liting Zheng: Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, 511436, China.
  3. Yiguo Jiang: Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, 511436, China. jiangyiguo@vip.163.com.
PMID: 38277035 DOI: 10.1007/s10534-023-00581-y

Abstract

Cadmium (Cd) is an important environmental pollutant that poses a threat to human health and represents a critical component of air pollutants, food sources, and cigarette smoke. Cd is a known carcinogen and has toxic effects on the environment and various organs in humans. Heavy metals within an organism are difficult to biodegrade, and those that enter the respiratory tract are difficult to remove. Autophagy is a key mechanism for counteracting extracellular (microorganisms and foreign bodies) or intracellular (damaged organelles and proteins that cannot be degraded by the proteasome) stress and represents a self-protective mechanism for eukaryotes against heavy metal toxicity. Autophagy maintains cellular homeostasis by isolating and gathering information about foreign chemicals associated with other molecular events. However, autophagy may trigger cell death under certain pathological conditions, including cancer. Autophagy dysfunction is one of the main mechanisms underlying Cd-induced cytotoxicity. In this review, the toxic effects of Cd-induced autophagy on different human organ systems were evaluated, with a focus on hepatotoxicity, nephrotoxicity, respiratory toxicity, and neurotoxicity. This review also highlighted the classical molecular pathways of Cd-induced autophagy, including the ROS-dependent signaling pathways, endoplasmic reticulum (ER) stress pathway, Mammalian target of rapamycin (mTOR) pathway, Beclin-1 and Bcl-2 family, and recently identified molecules associated with Cd. Moreover, research directions for Cd toxicity regarding autophagic function were proposed. This review presents the latest theories to comprehensively reveal autophagy behavior in response to Cd toxicity and proposes novel potential autophagy-targeted prevention and treatment strategies for Cd toxicity and Cd-associated diseases in humans.

Keywords

Autophagy Cadmium Cell fate Toxic mechanism

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Grants

  1. 81973086/National Natural Science Foundation of China
  2. 2023A1515010542/GuangDong Basic and Applied Basic Research Foundation

MeSH Term

Autophagy
Humans
Cadmium
Animals
Endoplasmic Reticulum Stress
Signal Transduction
Environmental Pollutants
Journal Article Review

Word Cloud

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