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Updated: Aug 11, 2026
Functional Neuroimaging Using Ultrasonic Blood-brain Barrier Disruption and Manganese-enhanced MRI
Published on: July 12, 2012
Changes in the brain mitochondrial proteome of male Sprague-Dawley rats treated with manganese chloride
Surong Zhang1, Juanling Fu, Zongcan Zhou
1Department of Toxicology, School of Public Health, Peking University Health Science Center, Beijing 100083, China.
Abstract:
To probe the mitochondrial involvement in Mn intoxicity, aliquots of brain mitochondria samples from control and treated (30 mg/kg manganese chloride, ip) male Sprague-Dawley rats were separated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and searched for protein abundance changes induced by Mn exposure. The electrophoretic separation resolved over 300 distinct spots as visualized by colloidal Coomassie blue (CCB), of which three spots were induced and three spots were inhibited after Mn exposure in all the five brain mitochondria preparations. Analysis by matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) indicated that these spots are calcium-transporting ATPase type 2C (ATP-dependent Ca(2+) pump PMR1); 60-kDa heat shock protein; Mitochondrial transmembrane GTPase FZO1B; ATP-binding cassette, sub-family b; Long-chain-fatty-acid-CoA ligase; ATP Synthase Beta Chain; and Succinate dehydrogenase flavoprotein subunit. The changes of the mitochondrial ATP synthase beta-subunit and Succinate dehydrogenase flavoprotein subunit indicate an effected level of mitochondrial ATP content and/or ATP-producing capacity. This result provides suggestion that respiratory chain complexes were implicated in the mitochondrial dysfunction induced by Mn intoxicity. And the changes of 60-kDa heat shock protein and ATP-dependent Ca(2+) pump PMR1 expression indicate that the Ca homeostasis and stress effect were involved in Mn intoxicity.
Insights
Manganese (Mn) exposure alters key mitochondrial proteins, affecting ATP production and calcium homeostasis. This suggests respiratory chain complexes and stress responses are involved in manganese toxicity.
Area of Science:
- Biochemistry
- Neuroscience
- Toxicology
Background:
- Manganese (Mn) is an essential trace element, but excessive exposure can lead to neurotoxicity.
- Mitochondrial dysfunction is increasingly recognized as a key mechanism in Mn intoxication.
- Understanding specific protein alterations in brain mitochondria is crucial for elucidating Mn toxicity pathways.
Purpose of the Study:
- To investigate the impact of Mn exposure on protein expression in rat brain mitochondria.
- To identify specific mitochondrial proteins affected by Mn intoxication.
- To explore the role of these protein changes in Mn-induced mitochondrial dysfunction.
Main Methods:
- Brain mitochondria were isolated from control and Mn-treated Sprague-Dawley rats.
- Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) was used to separate proteins.
- Matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry identified protein changes.
Main Results:
- Mn exposure altered the abundance of several mitochondrial proteins, including ATP synthase beta-subunit and succinate dehydrogenase flavoprotein subunit.
- Changes in these proteins suggest impaired mitochondrial ATP production and respiratory function.
- Increased expression of 60-kDa heat shock protein and ATP-dependent Ca(2+) pump PMR1 indicates involvement of calcium homeostasis and cellular stress responses.
Conclusions:
- Manganese toxicity significantly affects mitochondrial protein expression in the brain.
- Mitochondrial dysfunction in Mn intoxication involves alterations in energy production and calcium regulation.
- Respiratory chain complexes and stress response pathways are implicated in the neurotoxic effects of manganese.
