Related Experiment Video
Updated: Jul 14, 2026
07:55
Subcellular Fractionation for ERK Activation Upon Mitochondrial-derived Peptide Treatment
Published on: September 25, 2017
6-Hydroxydopamine induces mitochondrial ERK activation.
Scott M Kulich1, Craig Horbinski, Manisha Patel
1Department of Pathology, VA Pittsburgh Healthcare System, Pittsburgh, PA 15240, USA. kulichsm@upmc.edu
Free Radical Biology & Medicine
|July 3, 2007
Summary
Reactive oxygen species (ROS) contribute to 6-hydroxydopamine (6-OHDA) neuronal injury. Mitochondrial ERK activation plays a key role in this oxidative stress, making cells resistant to rescue therapies.
Area of Science:
- Neuroscience
- Cell Biology
- Toxicology
Background:
- Reactive oxygen species (ROS) are linked to 6-hydroxydopamine (6-OHDA) induced injury in catecholaminergic neurons.
- The precise mechanisms underlying 6-OHDA neurotoxicity, particularly the role of secondary ROS generation, remain unclear.
Purpose of the Study:
- To elucidate the mechanisms of 6-hydroxydopamine (6-OHDA) induced oxidative stress and neuronal injury.
- To investigate the role of reactive oxygen species (ROS) and ERK pathway activation in 6-OHDA neurotoxicity.
Main Methods:
- Utilized a neuronal cell line exposed to 6-hydroxydopamine (6-OHDA).
- Administered antioxidants (metalloporphyrins, catalase) at different time points post-exposure.
- Assessed ERK phosphorylation, aconitase inactivation, and mitochondrial ROS production (MitoSOX red).
Main Results:
- Catalytic metalloporphyrins protected cells if added within 1 hour, while catalase was effective only within 15 minutes of 6-OHDA exposure.
- A temporal link was observed between antioxidant efficacy loss and reduced inhibition of 6-OHDA-induced ERK phosphorylation.
- Early intracellular ROS were followed by delayed mitochondrial ROS production, coinciding with mitochondrial ERK activation and refractoriness to antioxidant rescue.
Conclusions:
- Mitochondrial reactive oxygen species (ROS) generation and subsequent extracellular signal-regulated kinase (ERK) pathway activation are critical in 6-hydroxydopamine (6-OHDA) neurotoxicity.
- This mitochondrial ERK activation renders 6-OHDA-injured neurons refractory to antioxidant intervention.
- Findings implicate mitochondrial ERK activation in Parkinsonian oxidative neuronal injury, aligning with observations in human Parkinson's disease neurons.
Related Concept Videos
01:29Drugs 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, which converts...
01:46Electron 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...
ROS generation is regulated and maintained at moderate levels necessary...
01:07MAPK 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...