Manganese accumulates primarily in nuclei of cultured brain cells

Abstract

Manganese (Mn) is known to pass across the blood-brain barrier and interact with dopaminergic neurons. However, the knowledge on the subcellular distribution of Mn in these cell types upon exposure to Mn remained incomplete. This study was designed to investigate the subcellular distribution of Mn in blood-brain barrier endothelial RBE4 cells, blood-cerebrospinal fluid barrier choroidal epithelial Z310 cells, mesencephalic dopaminergic neuronal N27 cells, and pheochromocytoma dopaminergic PC12 cells. The cells were incubated with 100 µM MnCl 2 with radioactive tracer 54 Mn in the culture media for 24 hrs. The subcellular organelles, i.e., nuclei, mitochondria, microsomes, and cytoplasm, were isolated by centrifugation and verified for their authenticity by determining the markers specific to cellular organelles. Data indicated that maximum Mn accumulation was observed in PC12 cells, which was 2.8, 5.2 and 5.9 fold higher than that in N27, Z310 and RBE4 cells, respectively. Within cells, about 92%, 72%, and 52% of intracellular 54 Mn were found to be present in nuclei of RBE4, Z310, and N27 cells, respectively. The recovery of 54 Mn in nuclei and cytoplasm of PC12 cells were 27% and 69% respectively. Surprisingly, less than 0.5% and 2.5% of cellular 54 Mn was found in mitochondrial and microsomal fractions, respectively. This study suggests that the nuclei may serve as the primary pool for intracellular Mn; mitochondria and microsomes may play an insignificant role in Mn subcellular distribution.

Functional MRI characterization of isolated human islet activation

“…Recent studies have linked Mn-induced changes in T 1 relaxation rates (DR 1 ) to intracellular Mn content in rat brain, and have found a linear correlation between R 1 and Mn concentrations obtained from tissue homogenates (36,37). These data, however, cannot be applied to the present study to extrapolate Mn concentrations, as different cell types have been found to sequester intracellular Mn very differently (38). In brain cells, Mn preferentially accumulates in the nuclei.…”

Manganese Accumulates within Golgi Apparatus in Dopaminergic Cells as Revealed by Synchrotron X-ray Fluorescence Nanoimaging

“…b p < 0.01. Article to occur (13). Using the direct chemical imaging nano-SXRF method, we evidenced that Mn is located principally within the Golgi apparatus of PC12 cells cultured in normal conditions, without adding Mn to the culture medium ( Figure 3).…”

“…It is generally accepted that Mn accumulates within the mitochondria of neuronal cells (11,12). However, a recent report suggests that less than 0.5% of intracellular Mn is found in the mitochondrial fraction and that Mn rather accumulates into the nucleus and cytoplasm of PC12 cells (13).…”

Acquired hepatocerebral degeneration

“…It is also unclear how the manganese causes neural damage. Some studies have found that the metal accumulates in high concentrations within the mitochondria of glial cells and that symptoms may be the result of disrupted energy metabolism [101], but data in this arena remain discordant [39,57].…”