The Presence of A manganese‐rich particle in lysosome of rat pancreas due to excess manganese treatment

Okamoto, Yoshihiro; Oshima, Reiko; Inagaki, Kazuhiro; Aita, Saburo; Nisioka, Hideo; Kondo, Yumi; Ishizuka, Hiroshi; Takada, Jitsuya; Nishida, Mikio

doi:10.1080/15216549700201401

Cited by 3 publications

(3 citation statements)

References 2 publications

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“…Nonetheless, only a handful of studies so far have investigated distribution of the element in the organ with no distinction between exocrine and endocrine components. Mn was found to accumulate primarily in lysosomes where it is bound to pro‐carboxypeptidase B, a zymogen found in the exocrine portion of the pancreas . Two studies on isolated rodent pancreatic islets used Mn to study Ca handling in β ‐cells and found a significant Mn uptake following glucose stimulation in all fractions, except for microsomes, with the mitochondrial fraction having the highest percentage increase .…”

Section: Discussionmentioning

confidence: 99%

“…When considering the in vivo application of MEMRI to pancreatic islets, the organ anatomy is a further complication. In the pancreas the β ‐cell‐rich endocrine tissue is highly dispersed within the acinar exocrine tissue, which has high affinity for Mn . In rodents, the acquisition of good high‐resolution images of the pancreas that allow discernment of the two tissue components is hindered by respiratory motion and by low tissue density.…”

Section: Discussionmentioning

confidence: 99%

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β‐Cell subcellular localization of glucose‐stimulated Mn uptake by X‐ray fluorescence microscopy: implications for pancreatic MRI

Leoni

Dhyani

Rivière

et al. 2011

Contrast Media & Molecular

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Manganese (Mn) is a calcium (Ca) analog that has long been used as a magnetic resonance imaging (MRI) contrast agent for investigating cardiac tissue functionality, for brain mapping and for neuronal tract tracing studies. Recently, we have extended its use to investigate pancreatic β-cells and showed that, in the presence of MnCl2, glucose activated pancreatic islets yield significant signal enhancement in T1-weigheted MR images. In this study, we exploited for the first time the unique capabilities of X-ray fluorescence microscopy (XFM) to both visualize and quantify the metal in pancreatic β-cells at cellular and sub-cellular levels. MIN-6 insulinoma cells grown in standard tissue culture conditions had only a trace amount of Mn, 1.14 ± 0.03 ×10-11 μg/μm2, homogenously distributed across the cell. Exposure to 2mM glucose and 50 μM MnCl2 for 20 minutes resulted in non-glucose dependent Mn uptake and the overall cell concentration increased to 8.99 ± 2.69 ×10-11 μg/μm2. When cells were activated by incubation in 16mM glucose in the presence of 50 μM MnCl2, a significant increase in cytoplasmic Mn was measured reaching 2.57 ± 1.34 ×10-10 μg/μm2. A further rise in intracellular concentration was measured following KCl induced depolarization, with concentrations totaling 1.25 ± 0.33 ×10-9 and 4.02 ± 0.71 ×10-10 μg/μm2 in the cytoplasm and nuclei respectively. In both activated conditions Mn was prevalent in the cytoplasm and localized primarily in a perinuclear region, possibly corresponding to the Golgi apparatus and involving the secretory pathway. These data are consistent with our previous MRI findings confirming that Mn can be used as a functional imaging reporter of pancreatic β-cell activation and also provide a basis for understanding how subcellular localization of Mn will impact MRI contrast

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

β‐Cell subcellular localization of glucose‐stimulated Mn uptake by X‐ray fluorescence microscopy: implications for pancreatic MRI

Leoni

Dhyani

Rivière

et al. 2011

Contrast Media & Molecular

View full text Add to dashboard Cite

show abstract

“…Lysosomes regulate cellular micro‐environmental homeostasis by trans‐lysosomal membrane transports and fusion with other subcellular structures. Interestingly, while Mn 2+ entry into and exit out of lysosomes require cross‐membrane transport machineries, lysosomal Mn 2+ is exported out of cells with vesicular fusions with plasma membrane, and while lysosomal Mn 2+ is transported into the cytoplasm with concentration difference, Mn 2+ is transported into lysosome from the cytoplasm by inverse concentration difference …”

Section: Lysosomal Handling Of Trace Metals and Lipidsmentioning

confidence: 99%

Impulse control disorder, lysosomal malfunction andATP13A2 insufficiency in Parkinsonism

Liu

Lü

et al. 2017

Clin Exp Pharma Physio

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Lysosomal transport of cargos in neurons is essential for neuronal proteostasis, transmission and functional motors and behaviours. Lysosomal malfunction including storage disorders is involved in the pathogenesis of Parkinson's disease (PD). Given the unclear molecular mechanisms of diverse defects in PD phenotypes, especially behavioural deficits, this mini review explores the cellular contexts of PD impulse control disorders and the molecular aspects of lysosomal cross-membrane transports. Focuses are paid to trace metal involvements in α-synuclein assembly in Lewy bodies, the func- The progressive neurodegeneration of specific brain regions has been shown to be associated with eosinophilic inclusions (Lewy bodies) in the neurons, resulting in reduced levels of DA in the striatum, loss of neuronal function, degeneration and death. Although dopaminergic neurotransmitter therapy can cause partial remission, it can also cause side effects including behavioural abnormalities. 1,2Parkinson's disease patients present the symptoms of behavioural disorder that include excessive eating, frequent sexual activity and other compulsive actions, characteristic of involuntary impulse control disorders that are clinically known as the impulse control disorder (ICD).2-4 Although its pathogenesis is unknown, ICD has been reported to be a common behavioural disorder accounting for 3% of adults usually in the youth stage 5 and 25%-50% in PD patients. [6][7][8] Clinical diagnosis of ICD depends on interrogation assessment, and apparently there is no effective treatment. [6][7][8] Understanding of the pathological changes of PD and ICD involves clarification of the concurrences of abnormal behaviour and movement mediated by convergent interactions between genetic and environmental factors on specified neurotransmitter circuits of particular brain regions. | THE CHARACTERISTICS OF PD ICDImpulsive control of behaviour is an important mechanism in the regulation of human and animal physiological behaviours, and is the result of the survival and evolution of social animals. For centuries, people

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Acute manganese treatment restores defective autophagic cargo loading in Huntington’s disease cell lines

Bryan

O’Brien

Nordham

et al. 2019

Human Molecular Genetics

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The molecular etiology linking the pathogenic mutations in the Huntingtin (Htt) gene with Huntington’s disease (HD) is unknown. Prior work suggests a role for Htt in neuronal autophagic function and mutant HTT protein disrupts autophagic cargo loading. Reductions in the bioavailability of the essential metal manganese (Mn) are seen in models of HD. Excess cellular Mn impacts autophagic function, but the target and molecular basis of these changes are unknown. Thus, we sought to determine if changes in cellular Mn status impact autophagic processes in a wild-type or mutant Htt-dependent manner. We report that the HD genotype is associated with reduced Mn-induced autophagy and that acute Mn exposure increases autophagosome induction/formation. To determine if a deficit in bioavailable Mn is mechanistically linked to the autophagy-related HD cellular phenotypes, we examined autophagosomes by electron microscopy. We observed that a 24 h 100 uM Mn restoration treatment protocol attenuated an established HD ‘cargo-recognition failure’ in the STHdh HD model cells by increasing the percentage of filled autophagosomes. Mn restoration had no effect on HTT aggregate number, but a 72 h co-treatment with chloroquine (CQ) in GFP-72Q-expressing HEK293 cells increased the number of visible aggregates in a dose-dependent manner. As CQ prevents autophagic degradation this indicates that Mn restoration in HD cell models facilitates incorporation of aggregates into autophagosomes. Together, these findings suggest that defective Mn homeostasis in HD models is upstream of the impaired autophagic flux and provide proof-of-principle support for increasing bioavailable Mn in HD to restore autophagic function and promote aggregate clearance.

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The Presence of A manganese‐rich particle in lysosome of rat pancreas due to excess manganese treatment

Cited by 3 publications

References 2 publications

β‐Cell subcellular localization of glucose‐stimulated Mn uptake by X‐ray fluorescence microscopy: implications for pancreatic MRI

β‐Cell subcellular localization of glucose‐stimulated Mn uptake by X‐ray fluorescence microscopy: implications for pancreatic MRI

Impulse control disorder, lysosomal malfunction andATP13A2 insufficiency in Parkinsonism

Acute manganese treatment restores defective autophagic cargo loading in Huntington’s disease cell lines

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