Manganese induces endoplasmic reticulum (ER) stress and activates multiple caspases in nigral dopaminergic neuronal

Related Experiment Video

Updated: Aug 15, 2026

Measurements of Physiological Stress Responses in C. Elegans
10:36

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

H S Chun1, H Lee, J H Son

  • 1Department of Neurology and Neuroscience, Weill Medical College of Cornell University at The W.M. Burke Medical Research Institute, White Plains, New York, NY 10605, USA.

Neuroscience Letters
|November 27, 2001
PubMed

Insights

Chronic manganese exposure causes Parkinson's disease (PD)-like symptoms. Manganese neurotoxicity involves endoplasmic reticulum stress and is reduced by Bcl-2 in dopaminergic neurons.

Area of Science:

  • Neuroscience
  • Toxicology
  • Cell Biology

Background:

  • Chronic manganese exposure is linked to Parkinson's disease (PD)-like symptoms.
  • Occupational manganese exposure is a potential risk factor for idiopathic PD.

Purpose of the Study:

  • Investigate the mechanism of manganese neurotoxicity in nigral dopaminergic (DA) neurons.
  • Determine the role of endoplasmic reticulum (ER) stress and Bcl-2 in manganese-induced DA cell death.

Main Methods:

  • Utilized the SN4741 dopaminergic cell line for experiments.
  • Assessed ER stress markers (BiP, caspase-12) and caspase activation (caspase-1, -8, -9, -3).
  • Examined the effect of Bcl-2 overexpression on manganese neurotoxicity.

Main Results:

  • Manganese treatment induced ER stress responses, including increased BiP and caspase-12 activation.
  • Manganese activated initiator caspases (-1, -8, -9) leading to caspase-3 activation and DA cell death.
  • Bcl-2 overexpression significantly reduced manganese-induced neurotoxicity in DA cells.

Conclusions:

  • Manganese-induced neurotoxicity in dopaminergic neurons is partly mediated by endoplasmic reticulum stress.
  • Bcl-2 overexpression offers significant protection against manganese neurotoxicity in DA cells.

More Related Videos

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons10:50

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons

Published on: April 24, 2021

Quantitative Analysis of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Stabilization in a Neural Model of Alzheimer's Disease (AD)06:41

Quantitative Analysis of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Stabilization in a Neural Model of Alzheimer's Disease (AD)

Published on: January 10, 2025

Related Concept Videos

Role of ER in the Secretory Pathway01:17

Role of ER in the Secretory Pathway

Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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...