The distribution of cathepsin D in rat tissues determined by immunocytochemistry

Whitaker, John N.; Rhodes, Roy H.

doi:10.1002/aja.1001660404

Cited by 43 publications

(18 citation statements)

References 39 publications

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“…CD is variably expressed in all tissues and is abundantly expressed in the brain (Whitaker and Rhodes, 1983;Reid et al, 1986). Mice deficient in CD die by postnatal day 26 (P26) Ϯ 1 from failure to thrive, triggered by intestinal necrosis, thromboembolia, and lymphopenia (Saftig et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Cathepsin D Deficiency Induces Persistent Neurodegeneration in the Absence of Bax-Dependent Apoptosis

Shacka¹,

Klocke²,

Young³

et al. 2007

J. Neurosci.

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Neuronal ceroid lipofuscinosces/Batten disease (NCL) is a devastating group of neurodegenerative diseases caused by genetic disrup 3-II, a selective autophagosome marker), respectively. Bax deletion significantly inhibited caspase-3 activation and hippocampal TUNEL reactivity but did not prevent the majority of CD deficiency-induced neuropathology, including the persistence of pyknotic neurons, elevated cortical TUNEL reactivity, lysosome dysfunction and autophagic stress, neurodegeneration, and neuron loss. Together, these results suggest that CD deficiency-induced neuropathology does not require Bax-dependent apoptosis and highlights the importance of caspase-independent neuron death and neurodegeneration resulting from the genetic disruption of lysosome function.

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Section: Introductionmentioning

confidence: 99%

Cathepsin D Deficiency Induces Persistent Neurodegeneration in the Absence of Bax-Dependent Apoptosis

Shacka¹,

Klocke²,

Young³

et al. 2007

J. Neurosci.

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“…The expression level of CD varies depending on the tissue, whereas neurons in CNS tissues possess abundant CD (Whitaker and Rhodes, 1983;Reid et al, 1986). It has been suggested that CD participates in various biological events such as the degradation of various brain-specific antigens, aging, and certain pathological situations in brain tissues (Banay-Schwartz et al, 1987;Matus and Green, 1987;Nakanishi et al, 1994Nakanishi et al, , 1997Cataldo et al, 1995).…”

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confidence: 99%

Cathepsin D Deficiency Induces Lysosomal Storage with Ceroid Lipofuscin in Mouse CNS Neurons

et al. 2000

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Cathepsin D-deficient (CDϪ/Ϫ) mice have been shown to manifest seizures and become blind near the terminal stage [approximately postnatal day (P) 26]. We therefore examined the morphological, immunocytochemical, and biochemical features of CNS tissues of these mice. By electron microscopy, autophagosome/ autolysosome-like bodies containing part of the cytoplasm, granular osmiophilic deposits, and fingerprint profiles were demonstrated in the neuronal perikarya of CDϪ/Ϫ mouse brains after P20. Autophagosomes and granular osmiophilic deposits were detected in neurons at P0 but were few in number, whereas they increased in the neuronal perikarya within days after birth. Some large-sized neurons having autophagosome/autolysosome-like bodies in the perikarya appeared in the CNS tissues, especially in the thalamic region and the cerebral cortex, at P17. These lysosomal bodies occupied the perikarya of almost all neurons in CDϪ/Ϫ mouse brains obtained from P23 until the terminal stage. Because these neurons exhibited autofluorescence, it was considered that ceroid lipofuscin may accumulate in lysosomal structures of CDϪ/Ϫ neurons. Subunit c of mitochondrial ATP synthase was found to accumulate in the lysosomes of neurons, although the activity of tripeptidyl peptidase-I significantly increased in the brain. Moreover, neurons near the terminal stage were often shrunken and possessed irregular nuclei through which small dense chromatin masses were scattered. These results suggest that the CNS neurons in CDϪ/Ϫ mice show a new form of lysosomal accumulation disease with a phenotype resembling neuronal ceroid lipofuscinosis.

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“…However, with the development of inflammation, type A cells along with neutrophils and macrophages may release these proteases extracellularly, participating in the degradation of the joint tissue. Strong immunoreactivity for cathepsins was found in the type A cells of the synovial membrane, as well as in macrophages and Kupffer cells in which large amounts of cathepsins B and D are contained (4,11,27,28). In the present study, gold particles indicating cathepsins B and D were found in the amorphous vacuoles close to the lateral intercellular spaces between type A cells and facing the joint cavity.…”

Section: Discussionmentioning

confidence: 52%

Localization of Cathepsins B and D in the Synovial Lining Cells of the Normal Rat Temporomandibular Joint by Immuno-light and -electron Microscopy.

Kiyoshima

Kido

Tsukuba

et al. 1994

Acta Histochem. Cytochem

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The localization of cathepsins B and D in the synovial lining cells and distribution of the lining cells containing these cathepsins in the normal rat temporomandibular joint (TMJ) were examined immunocytochemically in thick (8-10 pm) and semithin (1 pm) cryosections with the avidin-biotin-peroxidase complex method and in ultrathin sections with the gold-labeled IgG method. In the thick sections, strong immunoreactivity for cathepsins B and D probably in the type A cells (not clear at this level), was observed simultaneously in the superficial layer of the synovial membrane. This reactivity was strong at the following portions of the synovial membrane located adjacent to the blood vessels: 1) at the anterior portion and 2) medial-posterior portion facing the upper joint cavity, and 3) at the anterior portion and 4) lateral portion facing the lower joint cavity. In semithin cryosections, strong immunoreactivity for cathepsins B and D was simultaneously found in the type A cells which have numerous pseudopodia and vacuoles, while weak granular immunoreaction products for both cathepsins were also observed in the type B cells. In control sections, no type A or B cells showed immunoreactivity for these cathepsins. In the ultrathin sections, numerous gold particles indicating cathepsins B and D were detected in the lysosomes and phagolysosomes of the type A cells facing the lateral intercellular spaces and joint cavity.In the phagolysosomes, these cathepsins were characteristically co-localized. On the other hand, in the type B cells, a few gold particles were localized only in the lysosomes.Judging from these findings, it is suggested that type A cells predominantly contain cathepsins B and D, and that these cathepsins may be restricted within the cells (lysosomes) without extracellular release in the normal rat TMJ. It is also suggested that materials such as cell debris in the lateral intercellular spaces between the type A cells or in the joint cavity are endocytosed by phagosomes nearby, and are digested by proteolytic enzymes (cathepsins B and D) in the lysosomes. In addition, it is considered that this function in the type A cells is most conspicuous at the anterior portion of the synovial membrane of the normal rat TMJ.Cathepsins B, D and L have generally been associated with destructive diseases, because these enzymes can degrade various connective tissue components such as collagen (15) and proteoglycan (16,19). Besides its destructive ability, however, cathepsin D has the processing ability to activate procathepsins B and L (20), and cathepsin B also activates procollagenase (5). In particular, in arthritic knee joints, numerous investigators have reported that cathepsins B, D and L are expressed in the synovium, specifically in synovial lining cells (6,17,21,23).This synovial membrane consists of a synovial lining layer and a sublining layer. The synovial lining layer faces the joint cavity lying on the subliming layer and is mainly formed by two types of cells, type A (macrophage-like) and type B (fibrob...

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The distribution of cathepsin D in rat tissues determined by immunocytochemistry

Cited by 43 publications

References 39 publications

Cathepsin D Deficiency Induces Persistent Neurodegeneration in the Absence of Bax-Dependent Apoptosis

Cathepsin D Deficiency Induces Persistent Neurodegeneration in the Absence of Bax-Dependent Apoptosis

Cathepsin D Deficiency Induces Lysosomal Storage with Ceroid Lipofuscin in Mouse CNS Neurons

Localization of Cathepsins B and D in the Synovial Lining Cells of the Normal Rat Temporomandibular Joint by Immuno-light and -electron Microscopy.

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