Effects of Centrophenoxine on Lipofuscin Formation in Neuroblastoma Cells in Culture

Schneider, F. Howard; Nandy, Kalidas

doi:10.1093/geronj/32.2.132

Cited by 19 publications

(4 citation statements)

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“…However, the difficulties in studying aging phenomena in animals over relatively long periods of time have resulted in a scarcity of biochemical and pharmacological investigations on lipofuscin pigment. Recent studies on lipofuscin forma tion in vitro (11,16) have shown that cultured mouse neuroblastoma cells may provide a good model in which to study lipofuscin accumula tion and storage as well as how pharmacological agents may influence these events. These stud ies have shown that neuroblastoma lipofuscin pigment is similar to the pigment observed in mammalian neurons in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…Six 18 X 18 mm coverslips were contained in 10 ml of me dium in 100 X 15 mm plastic Petri dishes. Acid phosphatase activity was detected by the azo dye method; cytoplasmic clump formation of acid phos phatase-positive material was used as an indicator of lipofuscin (9,11,16). Lipofuscin content of the cultures was expressed as the percent of the cells counted (100-200) which contained acid phospha tase-positive clumps of material.…”

Section: Methodsmentioning

confidence: 99%

“…The deposition of lipofuscin pigment in nerve cells, as well as in other cells, is one of these age-related changes (8)(9)(10). Lipofuscin pigment also accumulates in nondividing neuro blastoma cells in culture as the cells age (11), and this in vitro model has been used to assess the ability of pharmacological agents to alter cell lipofuscin content (16).…”

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Effects of Hydergine on Aging Neuroblastoma Cells in Culture

Nandy¹,

Schneider²

1978

Pharmacology

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Exposure of mouse neuroblastoma cells in culture to low pH for 8 days caused a sixfold increase in cell lipofuscin pigment. Pigment content was measured as the percent of cells having clumps of acid phosphatase-staining material. Hydergine, bétwen 0.1 and 3 μg/ml, caused a concentration-related decrease in pigment content. Hydergine also stimulated neurite formation in cells in regular pH medium and was slightly toxic to cells in low pH medium. These results support the use of neuroblastoma cells as an in vitro model for age pigment studies.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Effects of Hydergine on Aging Neuroblastoma Cells in Culture

Nandy¹,

Schneider²

1978

Pharmacology

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“…In the study of lipofuscin, the cell culture system has been regarded as a useful model. Cultured cells such as neurons [8][9][10], glial cells [11,12], neuroblastoma cells [13][14][15], cardiac myocytes [7,[16][17][18][19] and fibroblasts [20] are known to accumulate lipofuscin within a short period. In our laboratory, we have tested some cell lines to study the mechanism of lipofuscin formation in neurons and found that NG108-15 cells cease proliferation and accumulate lipofuscin-like autofluorescent materials during neuronal differentiation.…”

Section: Introductionmentioning

confidence: 99%

Formation of Lipofuscin-Like Autofluorescent Materials in NG108-15 Cells: Involvement of Lysosomal Protein Degradation

Mochizuki

Park²,

Mori³

et al. 1997

Gerontology

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We found that neuroblastoma × glioma hybrid NG108-15 cells accumulated lipofuscin-like autofluorescent materials during neuronal differentiation in culture in a medium containing 1% fetal calf serum, 1 mM dibutyryl cyclic AMP and 1 mM theophylline. The emission maximum of the lipofuscin-like autofluorescent materials was between 500 and 550 nm. Granules positive to acid phosphatase and periodic-acid Schiff were increased, as were the autofluorescent granules in NG108-15 cells. Thiolprotease inhibitors, N-(L-3-trans-carboxyoxirane-2-carbonyl)-L-leucine-4-aminobutylamide (E-64) and acetyl-Leu-Leu-Arg (leupeptin), markedly accelerated the accumulation of the lipofuscin-like autofluorescent materials in NG108-15 cells. On the other hand, activities of lysosomal thiolproteases, cathepsin B, C and L, were increased during neuronal differentiation. Protein content in the cells was gradually increased with the neuronal differentiation, and the rise was significantly accelerated when proteolysis was inhibited by E-64. These results suggest that the lipofuscin-like autofluorescent materials contain peptidic substances as a component, and indicate that the increase in hydrolytic activities of thiolproteases during neuronal differentiation is not enough for the hydrolysis of peptidic substrates, resulting in the accumulation of autofluorescent materials in NG108-15 cells.

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