Mechanisms of lipofuscinogenesis: Effect of the inhibition of lysosomal proteinases and lipases under varying concentrations of ambient oxygen in cultured rat neonatal myocardial cells

Marzabadi, Massoud R.; Sohal, Rajindar S.; Brunk, Ulf T.

doi:10.1111/j.1699-0463.1991.tb05170.x

Cited by 40 publications

(16 citation statements)

References 38 publications

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“…This hypothesis is in agreement with the results of biochemical observations showing that orthophosphates and pyrophosphates are strong inhibitors of the lysosomal enzyme activity of earthworm chloragocytes (Varute and More 1973). It has been found that both inhibition of lysosomal hydrolases and oxidative stress play a significant role in lipofuscinogenesis (Marzabadi et al 1991).…”

Section: Discussionsupporting

confidence: 91%

Earthworm leukocyte populations specifically harbor lysosomal enzymes that may respond to bacterial challenge

Engelmann

Molńar

Pàlinkàs

et al. 2004

Cell and Tissue Research

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Earthworm leukocytes (coelomocytes) are responsible for innate cellular immune functions such as phagocytosis and encapsulation against parasites and pathogens. Microbial killing results from the combined action of the phagocytic process with humoral immune factors such as agglutinins (e.g., lectins), lysosomal enzymes (e.g., acid phosphatase, lysozyme), and various cytotoxic and antimicrobial molecules. There is also evidence of weak adaptive immune responses against foreign transplants. This study focused on aspects of the innate immune response. First, anti-human acid phosphatase (anti-AcP) polyclonal antibody characterized different acid hydrolase patterns in coelomocytes. Second, flow cytometry identified a strongly immunoreactive coelomocyte population. Third, ultrastructural and cytochemical analyses revealed acid phosphatase in discrete granules (lysosomes) of effector hyaline and granular coelomocytes but not in mature chloragocytes. Coelomocytes were exposed to bacteria to assess how phagocytosis influences: (a) the production of acid phosphatase using Western blot, and (b) release of acid phosphatase using ELISA from cell-free coelomic fluid. Fourth, after phagocytosis, acid phosphatase levels differed between controls and experimentals. Fifth, we found a 39-kDa molecule that reacted intensely with anti-AcP. Our results suggest that effector earthworm coelomocytes may not eliminate pathogens only by phagocytosis but also by extracellular lysis.

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Section: Discussionsupporting

confidence: 91%

Earthworm leukocyte populations specifically harbor lysosomal enzymes that may respond to bacterial challenge

Engelmann

Molńar

Pàlinkàs

et al. 2004

Cell and Tissue Research

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“…The accumulation of lipofuscin-like autofluorescent materials in NG108-15 cells was accelerated by the thiolprotease inhibitors E-64 and leupeptin, as reported previously for rat neurons [6] and cultured cardiac myocytes [7]. These results indicate that a decrease of the proteolytic activities during neuronal differentiation causes the formation of the materials in NG108-15 cells and suggest that some components in the materials must be peptidic substances.…”

Section: Discussionsupporting

confidence: 84%

“…Recently, it was reported that the activity of cathepsin B, which is the major lysosomal thiolprotease in rat brain [30,31], was not decreased with age [32]. Therefore, these 7 results also support the above-mentioned concept that an imbalance of proteolysis plays a part in lipofuscin formation in the rat neuron.…”

Section: Discussionsupporting

confidence: 77%

“…Many studies have indicated that oxidation is a causal factor in lipofuscin formation [5,7,16,17,19,27,33] and lipofuscin has been thought to be a highly conjugated lipid peroxidation product. However, in studies on retinal pigment epithelium (RPE) lipofuscin, it was elucidated that oxidation products of neural retina and RPE-choroid homogenates from young rats produced autofluorescence, but corrected autofluorescence spectra of those products were different from that of RPE lipofuscin [34].…”

Section: Discussionmentioning

confidence: 99%

“…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%

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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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Topographical localization of lipofuscin pigment in the brain of the aged fat-tailed dwarf lemur(Cheirogaleus Medius) and grey lesser mouse lemur(Microcebus Murinus): Comparison to iron localization

et al. 1999

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The present study was undertaken to explore the distribution of lipofuscin in the brain of cheirogaleids by autofluorescence and compare it to other studies of iron distribution. Aged dwarf (Cheirogaleus medius) and mouse (Microcebus murinus) lemurs provide a reliable model for the study of normal and pathological cerebral aging. Accumulation of lipofuscin, an age pigment derived by lipid peroxidation, constitutes the most reliable cytological change correlated with neuronal aging. Brain sections of four aged (8–15 year old) and 3 young (2–3 year old) animals were examined. Lipofuscin accumulation was observed in the aged animals but not in the young ones. Affected regions include the hippocampus (granular and pyramidal cells), where no iron accumulation was observed, the olfactory nucleus and the olfactory bulb (mitral cells), the basal forebrain, the hypothalamus, the cerebellum (Purkinje cells), the neocortex (essentially in the pyramidal cells), and the brainstem. Even though iron is known to catalyse lipid oxidation, our data indicate that iron deposits and lipofuscin accumulation are not coincident. Different biochemical and morphological cellular compartments might be involved in iron and lipofuscin deposition. The nonuniform distribution of lipofuscin indicates that brain structures are not equally sensitive to the factors causing lipofuscin accumulation. The small size, the rapid maturity, and the relatively short life expectancy of the cheirogaleids make them a good model system in which to investigate the mechanisms of lipofuscinogenesis in primates. Am. J. Primatol. 49:183–193, 1999. © 1999 Wiley‐Liss, Inc.

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Mechanisms of lipofuscinogenesis: Effect of the inhibition of lysosomal proteinases and lipases under varying concentrations of ambient oxygen in cultured rat neonatal myocardial cells

Cited by 40 publications

References 38 publications

Earthworm leukocyte populations specifically harbor lysosomal enzymes that may respond to bacterial challenge

Earthworm leukocyte populations specifically harbor lysosomal enzymes that may respond to bacterial challenge

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

Topographical localization of lipofuscin pigment in the brain of the aged fat-tailed dwarf lemur(Cheirogaleus Medius) and grey lesser mouse lemur(Microcebus Murinus): Comparison to iron localization

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