Manganese accumulates within golgi apparatus in dopaminergic cells as revealed by synchrotron X-ray fluorescence nanoimaging.
Chronic exposure to manganese results in neurological symptoms referred to as manganism and is identified as a risk factor for Parkinson's disease. In vitro, manganese induces cell death in the dopaminergic cells, but the mechanisms of manganese cytotoxicity are still unexplained. In particular, the subcellular distribution of manganese and its interaction with other trace elements needed to be assessed. Applying synchrotron X-ray fluorescence nanoimaging, we found that manganese was located within the Golgi apparatus of PC12 dopaminergic cells at physiologic concentrations. At increasing concentrations, manganese accumulates within the Golgi apparatus until cytotoxic concentrations are reached resulting in a higher cytoplasmic content probably after the Golgi apparatus storage capacity is exceeded. Cell exposure to manganese and brefeldin A, a molecule known to specifically cause the collapse of the Golgi apparatus, results in the striking intracellular redistribution of manganese, which accumulates in the cytoplasm and the nucleus. These results indicate that the Golgi apparatus plays an important role in the cellular detoxification of manganese. In addition manganese exposure induces a decrease in total iron content, which could contribute to the overall neurotoxicity.
Asunción
A
Carmona
Guillaume
G
Devès
Stéphane
S
Roudeau
Peter
P
Cloetens
Sylvain
S
Bohic
Richard
R
Ortega
D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D006706:Homeostasis / Q000502:physiology; D007501:Iron / Q000378:metabolism; D008345:Manganese / Q000378:metabolism*; D059906:Neuroimaging / Q000379:methods*; D016716:PC12 Cells; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D013052:Spectrometry, X-Ray Emission / Q000379:methods*; D017356:Synchrotrons; D013778:Tetrazolium Salts; D013844:Thiazoles; D014131:Trace Elements / Q000378:metabolism
D011500:Protein Synthesis Inhibitors; D013778:Tetrazolium Salts; D013844:Thiazoles; D014131:Trace Elements; D049452:Green Fluorescent Proteins; D020126:Brefeldin A; D008345:Manganese; D007501:Iron; C022616:thiazolyl blue