Involvement of cystatin C in oxidative stress-induced apoptosis of cultured rat CNS neurons

Nishio, Chika; Yoshida, Kiyomi; Nishiyama, Keiji; Hatanaka, Hiroshi; Yamada, Masashi

doi:10.1016/s0006-8993(00)02540-3

Cited by 52 publications

(48 citation statements)

References 46 publications

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“…Microarray data were confirmed by quantitative PCR, and further examined by in situ hybridization and immunohistochemistry. The results confirm earlier observations on the expression of cathepsin B (Bernstein, et al, 1989, Wasselius, et al, 2003 and cystatin C (Wasselius, et al, 2004, Wasselius, et al, 2001 by RPE cells, as well as, the induction of cystatin C by oxidative stress (Nishio, et al, 2000).…”

Section: Introductionsupporting

confidence: 91%

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Regulation of cysteine cathepsin expression by oxidative stress in the retinal pigment epithelium/choroid of the mouse

Alizadeh

Smit-McBride

Oltjen

et al. 2006

Experimental Eye Research

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Cystatin C is the major inhibitor of the cysteine cathepsins. Polymorphisms in the cystatin C gene have recently been associated with the risk of developing Age-related Macular Degeneration (AMD). Oxidative stress is also thought to play a key role in the pathogenesis of AMD. We surveyed the retinal pigment epithelium (RPE) and choroid of the C57BL/6J mouse for the expression of the cysteine cathepsins under normoxic and hyperoxic (75% O 2 ) conditions. Microarray analysis of RPE/ choroid mRNA revealed the expression of cathepsins B and L, as well as cystatin C under all experimental conditions. The microarray results were confirmed by real-time quantitative polymerase chain reaction (PCR). Localization of the mRNA species for cystatin C and cathepsin B, as well as, localization of protein species for cystatin C, cathepsin B and L were performed to evaluate the tissue distribution of these species.Our results indicate that cystatin C is largely synthesized in the RPE and secreted from the basal side. Cathepsin B is the major cysteine protease in the RPE and choroid. The expression of all mRNAs and proteins was elevated by exposure to oxidative stress.

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Section: Introductionsupporting

confidence: 91%

“…It has been previously reported that cystatin C expression is up-regulated by oxidative stress (Nishio et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Regulation of cysteine cathepsin expression by oxidative stress in the retinal pigment epithelium/choroid of the mouse

Alizadeh

Smit-McBride

Oltjen

et al. 2006

Experimental Eye Research

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“…In this regard, both beneficial and detrimental effects on neuronal survival have been attributed to extracellular proteases, including matrix metalloproteinases (MMPs) (53)(54)(55). Our study suggests that astrocytes are an important source of MMP inhibitors rather than MMPs.…”

Section: Discussionmentioning

confidence: 83%

Proteomic Analysis of Astrocytic Secretion in the Mouse

Lafon-Cazal

Adjali

Galéotti

et al. 2003

Journal of Biological Chemistry

132

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Astrocytes, the most abundant cell type in the central nervous system, are intimately associated with synapses. They play a pivotal role in neuronal survival and the brain inflammatory response. Some astrocytic functions are mediated by the secretion of polypeptides. Using a proteomic approach, we have identified more than 30 proteins released by cultured astrocytes. These include proteases and protease inhibitors, carrier proteins, and antioxidant proteins. Exposing astrocytes to brefeldin A, which selectively blocks secretory vesicle assembly, suppressed the release of some of these proteins. This indicates that astrocytes secrete these proteins by a classic vesicular mechanism and others by an alternative pathway. Astrocytes isolated from different brain regions secreted a similar pattern of proteins. However, the secretion of some of them, including metalloproteinase inhibitors and apolipoprotein E, was region-specific. In addition, pro-inflammatory treatments modified the profile of astrocytic protein secretion. Finally, more than two thirds of the proteins identified in the astrocyte-conditioned medium were detectable in the mouse cerebrospinal fluid, suggesting that astrocytes contribute to the cerebrospinal fluid protein content. In conclusion, this study provides the first unbiased characterization of the major proteins released by astrocytes, which may play a crucial role in the modulation of neuronal survival and function.Glial cells represent the largest cell population in the central nervous system (CNS).1 They are divided into three categories:astrocytes, the most abundant glial cell type, oligodendrocytes, the central equivalent of Schwann cells, and microglial cells, which share features with immune cells. For decades, astrocytes were essentially considered to be passive elements providing a structural support for neurons and contributing to the blood-brain barrier by wrapping processes around CNS microvessels. Several physiological properties related to CNS homeostasis (clearance and metabolism of neurotransmitters, regulation of extracellular pH, and K ϩ level) have also been attributed to astrocytes, which thereby contribute to the maintenance of an ideal environment for neuronal cell function (1).Many recent studies have established that astrocytes, which are intimately associated with synapses, are active integrators and regulators of neuronal activity and synaptic transmission (2-6). These astrocytic functions are mediated, at least in part, by the release of various substances, including amino acids and polypeptides. Indeed, glutamate released from synaptic terminals not only binds to glutamate receptors on the post-synaptic neurons but also activates ␣-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors on the surrounding astrocytes. This activation induces a rapid increase in intracellular Ca 2ϩ and a Ca 2ϩ -dependent release of glutamate from astrocytes that in turn activates post-synaptic glutamate receptors on neighboring neurons, thereby enhancing excitatory synaptic transmi...

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“…In fact, loss-of-function mutations in the cystatin B gene cause a severe neurological disorder known as Unverricht-Lundoborg disease in humans (48,49) and myoclonic seizures and ataxia in mice (50,51), in which cerebellar granule cells appear to undergo apoptosis. In contrast, CstC has been reported to induce apoptosis in cultured rat neurons (52) and during mouse embryo implantation and placentation (53). The present study has also shown that Cst10 overexpression led to apoptosis in chondrocytes.…”

Section: Discussionmentioning

confidence: 99%

Cystatin 10, a Novel Chondrocyte-specific Protein, May Promote the Last Steps of the Chondrocyte Differentiation Pathway

Koshizuka¹,

Yamada²,

Hoshi

et al. 2003

Journal of Biological Chemistry

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This study attempts to characterize cystatin 10 (Cst10), which we recently identified as a novel protein implicated in endochondral ossification. Expression of Cst10 was specific to cartilage, localized in the cytosol of prehypertrophic and hypertrophic chondrocytes of the mouse growth plate. In the mouse chondrogenic cell line ATDC5, Cst10 expression preceded type X collagen expression and increased in synchrony with maturation. When we compared ATDC5 cells transfected with Cst10 cDNA with cells transfected with a mock vector, hypertrophic maturation and mineralization of chondrocytes were promoted by Cst10 gene overexpression in that type X collagen expression was observed earlier, and alizarin red staining was stronger. On the other hand, type II collagen expression and Alcian blue staining, both of which are markers of the early stage of chondrocyte differentiation, were similar in both cells. Overexpression of the Cst10 gene also caused fragmentation of nuclei, the appearance of annexin V, a change in the mitochondrial membrane potential, and activation of caspases. These results strongly suggest that Cst10 may play an important role in the last steps of the chondrocyte differentiation pathway as an inducer of maturation, followed by apoptosis of chondrocytes.

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Involvement of cystatin C in oxidative stress-induced apoptosis of cultured rat CNS neurons

Cited by 52 publications

References 46 publications

Regulation of cysteine cathepsin expression by oxidative stress in the retinal pigment epithelium/choroid of the mouse

Regulation of cysteine cathepsin expression by oxidative stress in the retinal pigment epithelium/choroid of the mouse

Proteomic Analysis of Astrocytic Secretion in the Mouse

Cystatin 10, a Novel Chondrocyte-specific Protein, May Promote the Last Steps of the Chondrocyte Differentiation Pathway

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