Developmental and pathological expression of peroxisomal enzymes: their relationship of d-bifunctional protein deficiency and Zellweger syndrome

Itoh, Masayuki; Suzuki, Yasuyuki; Akaboshi, Shinjiro; Zhang, Zhongyi; Miyabara, Shinichi; Takashima, Sachio

doi:10.1016/s0006-8993(99)02423-3

Cited by 27 publications

(20 citation statements)

References 30 publications

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“…However, we do know that peroxisomes carry out essential functions in brain and a faulty organelle has been associated to some human diseases characterized by neurologic deficits (Lazarow and Moser, 1995). This finding is not surprising, because some studies point to a close relationship between peroxisomal enzymatic activity and neuronal growth and myelinogenesis (Lazo et al, 1991;Itoh et al, 2000). Zellweger syndrome and X-linked adrenoleukodystrophy (ALD) are the main examples of the disorders that have promoted the study of the peroxisomal function in the developing brain (Pollard et al, 1995;Berger et al, 1999;Itoh et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Although these lipids are required for the normal formation of the myelin sheath, an excessive accumulation induces severe damage to the brain, and different studies have shown that proper peroxisomal ␤-oxidation in the developing brain is essential to regulate the steady-state level of the fatty acids. These evidences suggest an important role for peroxisomes in neuronal maturation and myelinogenesis (Lazo et al, 1991;Itoh et al, 2000;Knoll et al, 2000). In the future, as the number of new proteins located in the organelle increases, more links will presumably be established between them and human disorders of peroxisomal origin.…”

Section: Introductionmentioning

confidence: 98%

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Mouse PeP: A novel peroxisomal protein linked to myoblast differentiation and development

Ferrer-Martı́nez

Ruiz‐Lozano

Chien

2002

Developmental Dynamics

137

121

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The identification of several peroxisomal proteins in the past decade has deepened our understanding of the biology of peroxisomes and their involvement in human disorders. We report the cloning and expression pattern during the mouse development of a cDNA encoding a novel protein, named PeP, and show that its product is imported specifically to the peroxisome matrix in a variety of cell types. We also demonstrate that PeP is imported to the organelle through the PEX5 receptor pathway, which indicates that the C-terminal tripeptide SKI behaves as a type 1 peroxisomal targeting signal (PTS1). PeP expression is tightly regulated, as shown by Northern and in situ hybridization experiments. Thus during embryonic development in the mouse, PeP mRNA is detected almost exclusively in the skeletal muscle, whereas in adult mice, strong expression is also found in the heart and brain. In addition, PeP mRNA accumulation is induced after myoblast differentiation in vitro, when myotube formation is promoted. Sequence analysis reveals that PeP has no significant homology to any known protein, except for a short stretch of amino acids containing the fingerprint of the fibronectin type III superfamily, a domain present in proteins often related to molecular and cellular recognition and binding processes. Thus our data suggest a connection between the function of PeP and murine cell differentiation and development.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Mouse PeP: A novel peroxisomal protein linked to myoblast differentiation and development

Ferrer-Martı́nez

Ruiz‐Lozano

Chien

2002

Developmental Dynamics

137

121

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“…When peroxidase-based immunohistochemistry with long staining times was used for rat and human brain tissue, strong cytoplasmic staining artefacts were created in less optimal preparations (Miyawaki et al, 1995;Moreno et al, 1995Moreno et al, , 1999Itoh et al, 2000;Nardacci et al, 2004). Even in studies with good antigen retrieval and staining times, weak cytoplasmic labeling was still present when peroxisomes were sufficiently well visualized (Zaar et al, 2002;Schad et al, 2003).…”

Section: In Situ Detection Of Peroxisomes In Paraffin Sections Of Dismentioning

confidence: 99%

“…In rat and human brain, some peroxisomal matrix proteins have been localized in recent years (Houdou et al, 1991(Houdou et al, , 1993Miyawaki et al, 1995;Moreno et al, 1995Moreno et al, , 1999Itoh et al, 2000;Zaar et al, 2002;Schad et al, 2003;Nardacci et al, 2004). In these studies, however, detection of the antigen-antibody complexes was mainly done by light microscopic peroxidase-based immunohistochemistry associated with diffusion artefacts of the reaction product in the cytoplasm.…”

mentioning

confidence: 99%

Differential expression of peroxisomal matrix and membrane proteins during postnatal development of mouse brain

Ahlemeyer

Neubert

Kovacs

et al. 2007

J of Comparative Neurology

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In peroxisomal biogenesis disorders, serious neurological abnormalities can be observed in the patients and the respective knockout mouse models. As a prerequisite for a better understanding of the relationship between the absence of peroxisomes and the observed neuropathology, knowledge of the regional and cell-type specific distribution of peroxisomal proteins in mouse brain is necessary. Therefore, we investigated the expression of distinct peroxins, peroxisomal membrane and matrix proteins (e.g. Pex5p, Pex14p, Pex13p, PMP70, catalase, peroxisomal thiolase, Acox1, "SKL"-PTS1 proteins) by indirect immunofluorescence 1) in primary cultures of the medial neocortex, hippocampus, and cerebellum of newborn mice and 2) in paraffin sections of mouse brain of different ages (newborn-adult). Quantitative analysis revealed a comparable abundance (number/microm(2)) of peroxisomes in cultured neurons and astrocytes of all three brain regions. In contrast, catalase immunoreactivity was higher in cultured astrocytes than in neurons. In mouse brain tissue, the abundance of peroxisomes decreased by half during postnatal development, also exhibiting prominent differences between distinct brain regions and cell types. Catalase protein levels in neuronal peroxisomes, however, decreased much more strongly in the neocortex, CA1-3 areas of the hippocampus, dentate gyrus, cerebellar nuclei, and cerebellar cortex but remained high in Bergmann glia and other astrocytes, epithelial cells of the choroid plexus, and ependyma. Similar age-dependent changes were found for thiolase and Acox1 protein levels. Developmental changes were confirmed by Western blot analysis using enriched peroxisomal and cytosolic fractions of the brain tissue as well as by measurement of catalase activity.

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“…Peroxisomes were abundant in oligodendrocytes during myelination (Adamo et al, 1986). More recent immunohistochemical data indicated constant brain expression of peroxisomal proteins from the juvenile period into adulthood (Adamo et al, 1986;Imamura et al, 1994;Itoh et al, 1999Itoh et al, , 2000Huyghe et al, 2001;Ahlemeyer et al, 2007).…”

Section: Introductionmentioning

confidence: 97%

Absence of Functional Peroxisomes from Mouse CNS Causes Dysmyelination and Axon Degeneration

Hulshagen¹,

Krysko²,

Bottelbergs³

et al. 2008

J. Neurosci.

100

110

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Peroxisomal metabolism is essential for normal brain development both in men and in mice. Using conditional knock-out mice, we recently showed that peroxisome deficiency in liver has a severe and persistent impact on the formation of cortex and cerebellum, whereas absence of functional peroxisomes from the CNS only causes developmental delays without obvious alteration of brain architecture.We now report that a substantial fraction of the latter Nes-Pex5 knock-out mice survive into adulthood but develop progressive motoric and coordination problems, impaired exploration, and a deficit in cognition and die before the age of 6 months. Histopathologically, both the white and gray matter of the CNS displayed a region-specific accumulation of neutral lipids, astrogliosis and microgliosis, upregulation of catalase, and scattered cell death. Nes-Pex5 knock-out mice featured a dramatic reduction of myelin staining in corpus callosum, whereas cerebellum and other white matter tracts were less affected or unchanged. This was accompanied by a depletion of alkenylphospholipids in myelin and differentially reduced immunoreactivity of myelin proteins. EM analysis revealed that myelin wrappings around axons did still form, but they showed a reduction in thickness relative to axon diameters. Remarkably, multifocal axonal damage occurred in the corpus callosum. Thereby, debris accumulated between axolemma and inner myelin surface and axons collapsed, although myelin sheaths remained present. These anomalies of myelinated axons were already present in juvenile mice but aggravated in adulthood. Together, loss of CNS peroxisomal metabolism both affects myelin sheaths and axonal integrity possibly via independent pathways.

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Developmental and pathological expression of peroxisomal enzymes: their relationship of d-bifunctional protein deficiency and Zellweger syndrome

Cited by 27 publications

References 30 publications

Mouse PeP: A novel peroxisomal protein linked to myoblast differentiation and development

Mouse PeP: A novel peroxisomal protein linked to myoblast differentiation and development

Differential expression of peroxisomal matrix and membrane proteins during postnatal development of mouse brain

Absence of Functional Peroxisomes from Mouse CNS Causes Dysmyelination and Axon Degeneration

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