Related Experiment Video

Updated: Mar 20, 2026

Human Neural Organoids for Studying Brain Cancer and Neurodegenerative Diseases
09:36

Human Neural Organoids for Studying Brain Cancer and Neurodegenerative Diseases

Published on: June 28, 2019

10.7K

Cell cycle activation in p21 dependent pathway: An alternative mechanism of organophosphate induced dopaminergic

Willayat Yousuf Wani1, Ramesh J L Kandimalla2, Deep Raj Sharma1

  • 1Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.

Biochimica Et Biophysica Acta. Molecular Basis of Disease
|June 6, 2016
PubMed

Insights

Dichlorvos pesticide exposure causes oxidative stress and DNA damage in nerve cells, reactivating cell cycle processes and leading to programmed cell death (apoptosis) through caspase activation.

Area of Science:

  • Neuroscience
  • Toxicology
  • Cell Biology

Background:

  • Previous studies linked dichlorvos to oxidative stress and apoptosis in dopaminergic neurons.
  • The current study investigates dichlorvos's impact on cell cycle regulation in neuronal cells.

Purpose of the Study:

  • To elucidate the mechanism of dichlorvos-induced oxidative stress on cell cycle activation in differentiated PC12 cells.
  • To determine if dichlorvos exposure can cause differentiated cells to re-enter the cell cycle and undergo apoptosis.

Main Methods:

  • NGF-differentiated PC12 cells were exposed to dichlorvos.
  • Assessed oxidative DNA damage, cell cycle machinery activation (p53, cyclin-D1, pRb, p21), and cell cycle phase distribution using flow cytometry.
  • Immunoblotting was used to analyze proteins involved in apoptosis (cytochrome c, Bax, Bcl-2, cleaved caspase-3).

Main Results:

  • Dichlorvos exposure induced oxidative DNA damage and activated cell cycle proteins (increased p53, cyclin-D1, pRb; decreased p21).
  • Cell cycle analysis showed a shift from G0/G1 phase to S and G2/M phases in dichlorvos-treated cells.
  • Dichlorvos triggered caspase-dependent apoptosis, evidenced by cytochrome c release and caspase-3 activation.

Conclusions:

  • Dichlorvos-induced oxidative stress activates cell cycle machinery in differentiated PC12 cells, promoting cell cycle re-entry.
  • This process culminates in apoptotic cell death mediated by mitochondrial cytochrome c release and caspase-3 activation.
Keywords:
Cyclin-D1DichlorvosNeurodegenerationOxidative stressp21

More Related Videos

Primary Culture of Mouse Dopaminergic Neurons11:58

Primary Culture of Mouse Dopaminergic Neurons

Published on: September 8, 2014

39.8K
Quantifying Levels of Dopaminergic Neuron Morphological Alteration and Degeneration in Caenorhabditis elegans06:17

Quantifying Levels of Dopaminergic Neuron Morphological Alteration and Degeneration in Caenorhabditis elegans

Published on: November 20, 2021

5.0K

Related Concept Videos

Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.8K
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
3.3K
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
10.3K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.1K
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...
1.9K
Drugs Affecting Neurotransmitter Synthesis01:29

Drugs Affecting Neurotransmitter Synthesis

Drugs affecting neurotransmitter synthesis can impact the adrenergic neuron and the synthesis of neurotransmitters. For example, α-methyltyrosine and carbidopa target specific enzymes involved in catecholamine synthesis. α-methyltyrosine inhibits the enzyme tyrosine hydroxylase, which converts tyrosine into dopamine. By blocking this enzyme, α-methyltyrosine reduces dopamine production and other catecholamines. Carbidopa, on the other hand, inhibits the enzyme dopa decarboxylase,...
2.4K