Related Experiment Video

Updated: May 22, 2026

Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons
10:36

Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons

Published on: November 6, 2017

Arsenic induces apoptosis in myoblasts through a reactive oxygen species-induced endoplasmic reticulum stress and

Yuan-Peng Yen1, Keh-Sung Tsai, Ya-Wen Chen

  • 1College of Medicine, Institute of Toxicology, National Taiwan University, Taipei, Taiwan.

Archives of Toxicology
|May 25, 2012
PubMed

Insights

Arsenic trioxide induces skeletal muscle cell death by promoting apoptosis via oxidative stress, endoplasmic reticulum stress, and Akt pathway inactivation. N-acetylcysteine protects myoblasts by mitigating these toxic effects.

Area of Science:

  • Toxicology
  • Cell Biology
  • Muscle Physiology

Background:

  • Skeletal muscle size depends on myoblast availability for myogenesis.
  • Decreased myoblast proliferation or increased cytotoxicity can reduce muscle fibers.
  • Understanding toxicants that induce myoblast apoptosis is crucial for muscle development and regeneration.

Purpose of the Study:

  • To investigate the cytotoxic effects of arsenic trioxide (As(2)O(3)) on C2C12 myoblasts.
  • To elucidate the underlying mechanisms of As(2)O(3)-induced myoblast apoptosis.
  • To explore the protective role of N-acetylcysteine (NAC) against As(2)O(3) toxicity.

Main Methods:

  • C2C12 myoblasts were treated with varying concentrations of As(2)O(3).
  • Apoptosis markers, mitochondrial membrane potential, and caspase activity were assessed.
  • Endoplasmic reticulum (ER) stress markers were analyzed.
  • Reactive oxygen species (ROS) levels and Akt phosphorylation were measured.
  • The effects of NAC pretreatment and Akt over-expression were evaluated.

Main Results:

  • As(2)O(3) induced apoptosis in myoblasts, evidenced by increased Bax/Bcl-2 ratio, decreased mitochondrial potential, cytochrome c release, and caspase activation.
  • As(2)O(3) triggered ER stress, indicated by elevated GRP-78, GRP-94, PERK, eIF2α, ATF6, and caspase-12.
  • NAC pretreatment reduced ROS, lipid peroxidation, ER stress, caspase activity, and apoptosis.
  • As(2)O(3) decreased Akt phosphorylation, which was reversed by NAC and attenuated by Akt over-expression.

Conclusions:

  • Arsenic trioxide induces cytotoxicity in myoblasts by promoting apoptosis.
  • The mechanism involves ROS-induced mitochondrial dysfunction, ER stress, and Akt pathway inactivation.
  • N-acetylcysteine exhibits protective effects against As(2)O(3)-induced myoblast apoptosis.

Related Concept Videos

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...
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...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
Anticholinesterase Agents: Poisoning and Treatment01:26

Anticholinesterase Agents: Poisoning and Treatment

Anticholinesterases, also known as cholinesterase inhibitors, work by blocking the breakdown of acetylcholine, leading to its accumulation in the synaptic cleft. This accumulation indirectly enhances both muscarinic and nicotinic actions. These agents are classified as reversible or irreversible based on their mechanism of action.     
Irreversible agents form a strong bond with the cholinesterase enzyme, making it inactive. The breakdown of the phosphorylated enzyme is slower than the...
The Electron Transport Chain01:30

The Electron Transport Chain

The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q in...