Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plaque-like lesions and amyloid angiopathy were investigated in the frontal cerebral cortex of four patients with hereditary cerebral hemorrhage with amyloidosis (Dutch) (HCHWA-D), using immunohistochemical [antibodies to beta amyloid protein (A beta), beta protein precursor (beta PP), synaptophysin, ubiquitin (UBQ), cathepsin D, paired helical filaments (PHF) and glial fibrillary acidic protein (GFAP)], enzymehistochemical (acid phosphatase) and silver [methenamine silver (MS) and Palmgren] staining methods. Whereas A beta- and MS-positive diffuse plaques were found in all patients, only the three older patients showed neuritic or congophilic plaques, which were acid phosphatase and cathepsin D positive and contained beta PP-, synaptophysin- and UBQ-positive, but PHF-negative neurites. These plaques were surrounded by reactive astrocytes. Similar immuno- and enzymereactivity was found around congophilic blood vessels. Thus, apart from neuronal degeneration in a subset of plaque-like lesions and around blood vessels, this study shows an age-related morphology of the plaques in HCHWA-D, corresponding to that in Down's syndrome (DS), with the difference that neurofibrillary (NF) pathology is absent in HCHWA-D in contrast to DS. HCHWA-D may be considered as a model for congophilic plaque formation not associated with NF pathology.
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PMID:Hereditary cerebral hemorrhage with amyloidosis (Dutch): a model for congophilic plaque formation without neurofibrillary pathology. 783 31

Abnormalities of tubular matrix metalloproteinases have been shown recently to occur early in the course of polycystic kidney disease (PKD). The present study was conducted to determine whether lysosomal cysteine proteinases were altered in proximal tubules from 2-month-old, heterozygous Han:SPRD rats. The activities of cathepsins B (-45%), H (-39%) and L (-37%) were significantly lower in proximal tubules from PKD rats as compared to healthy offspring. Enzyme proteins were also decreased (cath. B, 2.4 +/- 0.7-fold; cath. H, 1.9 +/- 0.6-fold; N = 4, P < 0.05), while mRNA levels for cathepsins B, H and L were not different. Tubular cystatin C, a major inhibitor of cathepsins, was normal with regard to protein and mRNA levels in PKD animals. The decrease in cathepsins in PKD was specific for tubules, as enzyme activities in glomeruli and liver tissue were unchanged and limited to the lysosomal compartment, since marker enzymes for cytoplasm, endoplasmatic reticulum and mitochondria were all normal. Intralysosomally, soluble enzymes like cathepsins and beta-NAG were decreased, while membrane-bound acid phosphatase was unchanged. The presence of cathepsins could be demonstrated in cyst fluid from homozygous PKD rats and urinary excretion of cathepsins was enhanced in heterozygous animals. Taken together, these findings indicate that the reduction in tubular cathepsins B, H and L was neither due to decreased gene expression nor to upregulation of specific inhibitors, but was likely due to enhanced apical secretion of these enzymes.
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PMID:Alterations of cathepsins B, H and L in proximal tubules from polycystic kidneys of the Han:SPRD rat. 884 Feb 69

The induction of the formation of inclusion vesicles in Leishmania amazonensis by the sterol biosynthesis inhibitors (SBI) ketoconazole and terbinafine has been reported previously. These compartments were recently identified as acidocalcisomes. By the use of electron spectroscopic imaging and energy loss spectroscopy, the presence of calcium, phosphorus and oxygen in the electron-dense inclusions located within the acidocalcisomes has been demonstrated. Endoplasmic reticulum cisternae formed membrane whorls which enclosed large portions of the cytoplasm and sometimes circumscribed acidocalcisomes. In addition, acid phosphatase activity, as well as the endocytic tracers horseradish peroxidase and gold-labelled transferrin and cystatin C were detected within these organelles in both SBI-treated and untreated parasites. These data suggest that impairment of sterol biosynthesis induces the biogenesis of acidocalcisomes and triggers an autophagic process that leads to intersection of the endosomal/lysosomal system with the acidocalcisomes.
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PMID:Impairment of sterol biosynthesis leads to phosphorus and calcium accumulation in Leishmania acidocalcisomes. 1058 30

We have previously shown that chronic treatment of chick embryos [from embryonic day 5 (E5) to E9] with NMDA rescues spinal cord motoneurons (MNs) from programmed cell death. In this situation, MNs exhibit a reduced vulnerability to acute excitotoxic lesions and downregulate NMDA and AMPA-kainate receptors. Here, we report that this treatment results in long-lasting sublethal structural changes in MNs. In Nissl-stained sections from the spinal cord of NMDA-treated embryos, MNs display an area adjacent to an eccentrically positioned nucleus in which basophilia is excluded. Ultrastructurally, MNs accumulate tubulovesicular structures surrounded by Golgi stacks. Thiamine pyrophosphatase but not acid phosphatase was detected inside the tubulovesicular structures, which are resistant to disruption by brefeldin A or monensin. Immunocytochemistry reveals changes in the content and distribution of calcitonin gene-related peptide, the KDEL receptor, the early endosomal marker EEA1, and the recycling endosome marker Rab11, indicating that a dysfunction in membrane trafficking and protein sorting occurs in these MNs. FM1-43, a marker of the endocytic pathway, strongly accumulates in MNs from isolated spinal cords after chronic NMDA treatment. Changes in the distribution of cystatin C and presenilin-1 and an accumulation of amyloid precursor protein and beta-amyloid product were also observed in NMDA-treated MNs. None of these alterations involve an interruption of MN-target (muscle) connections, as detected by the retrograde tracing of MNs with cholera toxin B subunit. These results demonstrate that chronic NMDA treatment induces severe changes in the motoneuronal endomembrane system that may be related to some neuropathological alterations described in human MN disease.
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PMID:Long-lasting aberrant tubulovesicular membrane inclusions accumulate in developing motoneurons after a sublethal excitotoxic insult: a possible model for neuronal pathology in neurodegenerative disease. 1158 80