Related Experiment Video

Updated: Aug 7, 2026

Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model
08:15

Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model

Published on: June 6, 2025

Cadmium blocks receptor-mediated Jak/STAT signaling in neurons by oxidative stress

Richard K Monroe1, Stanley W Halvorsen

  • 1Program in Neurosciences, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, 102 Farber Hall, Buffalo, NY 14214-3000, USA.

Free Radical Biology & Medicine
|July 18, 2006
PubMed

Insights

Cadmium exposure inhibits crucial neuronal signaling pathways, specifically ciliary neurotrophic factor (CNTF)-mediated Jak/STAT signaling, by inducing oxidative stress. This discovery reveals a new mechanism for cadmium neurotoxicity and its potential role in neurodegenerative diseases.

Area of Science:

  • Neuroscience
  • Environmental Health
  • Toxicology

Background:

  • Cadmium is an environmental contaminant linked to neurological disorders.
  • The precise mechanisms of cadmium neurotoxicity remain incompletely understood.

Purpose of the Study:

  • To investigate how cadmium affects neuronal signaling pathways.
  • To elucidate the cellular mechanisms underlying cadmium-induced neurotoxicity.

Main Methods:

  • Utilized human BE(2)-C neuroblastoma cells and chick retina neurons.
  • Assessed inhibition of ciliary neurotrophic factor (CNTF)-mediated Jak1/Jak2 tyrosine kinase signaling.
  • Measured tyrosine phosphorylation of STAT1 and STAT3.
  • Evaluated cellular oxidative stress using dichlorofluorescein.
  • Tested the protective effects of antioxidants.

Main Results:

  • Cadmium chloride (CdCl2) significantly inhibited CNTF-induced Jak/STAT signaling in neuronal cells.
  • This inhibition occurred at low CdCl2 concentrations and short exposure times.
  • CdCl2 increased cellular oxidative stress, which was reversed by antioxidants.
  • Signaling in non-neuronal cells remained unaffected, indicating neuronal selectivity.

Conclusions:

  • Cadmium inhibits neuronal Jak/STAT signaling through oxidative stress, a novel mechanism of neurotoxicity.
  • This finding implicates cadmium as a potential environmental factor in neurodegenerative diseases.

Related Concept Videos

The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...