Localization of the Endogenous Cysteine Proteinase Inhibitor, Cystatin C, and the Cysteine Proteinase, Cathepsin B, to the Junctional Epithelium in Rat Gingiva

Yamaza, Takayoshi; Mino, Satoya; Atsuta, Ikiru; Danjo, Atsushi; Kagiya, Tadayoshi; Nishijima, Kiyoto; Zang, Jin Qi; Kido, Mizuho A.; Takano, Teruo

doi:10.1267/ahc.38.121

Cited by 4 publications

(2 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It contains 120 amino acids, and its molecular weight is 13 KDa [ 1 ]. CST3 is found to be localized in lysosomes [ 2 , 3 ], where it plays an important role in controlling the functions of the organelle by regulating the activity of cysteine protease enzymes including cathepsin B, H, and L [ 4 , 5 ]. It is also localized in the endoplasmic reticulum and Golgi complex, indicating it as a secreted protein [ 1 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Aggregation of Cystatin C Changes Its Inhibitory Functions on Protease Activities and Amyloid β Fibril Formation

Sheikh

Wada

Tabassum

et al. 2021

IJMS

View full text Add to dashboard Cite

Cystatin C (CST3) is an endogenous cysteine protease inhibitor, which is implicated in cerebral amyloid angiopathy (CAA). In CAA, CST3 is found to be aggregated. The purpose of this study is to investigate whether this aggregation could alter the activity of the protein relevant to the molecular pathology of CAA. A system of CST3 protein aggregation was established, and the aggregated protein was characterized. The results showed that CST3 aggregated both at 80 °C without agitation, and at 37 °C with agitation in a time-dependent manner. However, the levels of aggregation were high and appeared earlier at 80 °C. Dot-blot immunoassay for oligomers revealed that CST3 could make oligomeric aggregates at the 37 °C condition. Electron microscopy showed that CST3 could make short fibrillary aggregates at 37 °C. Cathepsin B activity assay demonstrated that aggregated CST3 inhibited the enzyme activity less efficiently at pH 5.5. At 7.4 pH, it lost the inhibitory properties almost completely. In addition, aggregated CST3 did not inhibit Aβ1-40 fibril formation, rather, it slightly increased it. CST3 immunocytochemistry showed that the protein was positive both in monomeric and aggregated CST3-treated neuronal culture. However, His6 immunocytochemistry revealed that the internalization of exogenous recombinant CST3 by an astrocytoma cell culture was higher when the protein was aggregated compared to its monomeric form. Finally, MTT cell viability assay showed that the aggregated form of CST3 was more toxic than the monomeric form. Thus, our results suggest that aggregation may result in a loss-of-function phenotype of CST3, which is toxic and responsible for cellular degeneration.

show abstract

Section: Introductionmentioning

confidence: 99%

Aggregation of Cystatin C Changes Its Inhibitory Functions on Protease Activities and Amyloid β Fibril Formation

Sheikh

Wada

Tabassum

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Cystatin C (CST3) is a 13-kDa protein consisting of 120 amino acids, encoded by a 7.3-kb gene located in chromosome 20 1 . It is expressed in all types of cells 2 , where it is located in the lysosome, Golgi apparatus and endoplasmic reticulum [3][4][5][6][7] . It is also a secreted protein and found in all types of body fluid 8 .…”

mentioning

confidence: 99%

Association between cystatin C gene polymorphism and the prevalence of white matter lesion in elderly healthy subjects

Maniwa

Yano

Sheikh

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Cystatin C (CST3) is a cysteine protease inhibitor abundant in the central nervous system, and demonstrated to have roles in several pathophysiological processes including vascular remodeling and inflammation. Previously, we showed a relation of CST3 gene polymorphisms with deep and subcortical white matter hyperintensity (DSWMH) in a small case-control study. In this study, we aimed to investigate the relation in a larger cross-sectional study. Participants of a brain health examination program were recruited (n = 1795) in the study, who underwent routine blood tests and cognitive function tests. Cerebral white matter changes were analyzed by MRI. Additionally, 7 single nucleotide polymorphisms (SNPs) (−82G/C, −78T/G, −5G/A, +4A/C, +87C/T, +148G/A and +213G/A) in the promoter and coding regions of CST3 gene were examined. Among them, carriers of the minor allele haplotype −82C/+4C/+148A were significantly associated with decreased CST3 concentration in the plasma. Unadjusted analysis did not show significant relation between carriers of the minor allele haplotype and periventricular hyperintensity (PVH), but DSWMH was marginally (p < 0.054) increased in this group. After adjusting the effects of other variables like age and kidney function, logistic regression analysis revealed that carriers of the minor allele haplotype were at a significantly increased risk of developing both pVH and DSWMH. thus, our results suggest that carriers of the minor allele haplotype −82C/+4C/+148A of CST3 gene could be at an increased risk to develop cerebral white matter disturbance.

show abstract

Some Advanced Biomarkers of Neurodegenerative Disorders: Focus on Cystatin C

Korolenko,

Pupyshev,

Belichenko

et al. 2023

Neurochem. J.

View full text Add to dashboard Cite

Localization of the Endogenous Cysteine Proteinase Inhibitor, Cystatin C, and the Cysteine Proteinase, Cathepsin B, to the Junctional Epithelium in Rat Gingiva

Cited by 4 publications

References 44 publications

Aggregation of Cystatin C Changes Its Inhibitory Functions on Protease Activities and Amyloid β Fibril Formation

Aggregation of Cystatin C Changes Its Inhibitory Functions on Protease Activities and Amyloid β Fibril Formation

Association between cystatin C gene polymorphism and the prevalence of white matter lesion in elderly healthy subjects

Some Advanced Biomarkers of Neurodegenerative Disorders: Focus on Cystatin C

Contact Info

Product

Resources

About