ArticleThe FEBS journal2008
Internalization of cystatin C in human cell lines.
Article in The FEBS journal, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
29 citing papers in PubMed, 55 citations in OpenAlex.
- Unravelling the Significance of Cystatin C and Bunina Bodies in Amyotrophic Lateral Sclerosis Pathogenesis.Neuropathology and applied neurobiology · 2026Review
- Age-dependent changes on fractalkine forms and their contribution to neurodegenerative diseases.Frontiers in molecular neuroscience · 2023Review
- Skin chronological aging drives age-related bone loss via secretion of cystatin-A.Nature aging · 2022Article
- Increased serum cystatin C levels and responses of pancreatic α- and β-cells in type 2 diabetes.Endocrine connections · 2022Article
- Aggregation of Cystatin C Changes Its Inhibitory Functions on Protease Activities and Amyloid β Fibril Formation.International journal of molecular sciences · 2021Article
- Cystatin C Deficiency Increases LPS-Induced Sepsis and NLRP3 Inflammasome Activation in Mice.Cells · 2021Article
- Externally added cystatin C reduces growth of A375 melanoma cells by increasing cell cycle time.FEBS open bio · 2021Article
- Pressure overload promotes cystatin C secretion of cardiomyocytes to regulate the MAPK signaling pathway and mediate cardiac hypertrophy.Annals of translational medicine · 2020Article
- Secreted cystatins decrease proliferation and enhance apoptosis of human leukemic cells.FEBS open bio · 2020Article
- Deubiquitinating Enzymes in Coronaviruses and Possible Therapeutic Opportunities for COVID-19.International journal of molecular sciences · 2020Review
- Cystatin C promotes cognitive dysfunction in rats with cerebral microbleeds by inhibiting the ERK/synapsin Ia/Ib pathway.Experimental and therapeutic medicine · 2020Article
- Characterization, Recombinant Production and Structure-Function Analysis of NvCI, A Picomolar Metallocarboxypeptidase Inhibitor from the Marine SnailMarine drugs · 2019Article
- Neuroprotection mediated by cystatin C-loaded extracellular vesicles.Scientific reports · 2019Article
- Cystatin C Expression is Promoted by VEGFA Blocking, With Inhibitory Effects on Endothelial Cell Angiogenic Functions Including Proliferation, Migration, and Chorioallantoic Membrane Angiogenesis.Journal of the American Heart Association · 2018Article
- Renal Biomarker and Angiostatic Mediator? Cystatin C as a Negative Regulator of Vascular Endothelial Cell Homeostasis and Angiogenesis.Journal of the American Heart Association · 2018Article
- Low-level internalization of cystatin E/M affects legumain activity and migration of melanoma cells.The Journal of biological chemistry · 2017Article
- Cystatin C in aging and in Alzheimer's disease.Ageing research reviews · 2016Review
- Differential cathepsin responses to inhibitor-induced feedback: E-64 and cystatin C elevate active cathepsin S and suppress active cathepsin L in breast cancer cells.The international journal of biochemistry & cell biology · 2016Article
- Cystatin C protects neuronal cells against mutant copper-zinc superoxide dismutase-mediated toxicity.Cell death & disease · 2014Article
- Cystatin C properties crucial for uptake and inhibition of intracellular target enzymes.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Altered protease activity is considered important for tumour invasion and metastasis, processes in which the cysteine proteases cathepsin B and L are involved. Their natural inhibitor cystatin C is a secreted protein, suggesting that it functions to control extracellular protease activity. Because cystatins added to cell cultures can inhibit polio, herpes simplex and coronavirus replication, which are intracellular processes, the internalization and intracellular regulation of cysteine proteases by cystatin C should be considered. The extension, mechanism and biological importance of this hypothetical process are unknown. We investigated whether internalization of cystatin C occurs in a set of human cell lines. Demonstrated by flow cytometry and confocal microscopy, A-431, MCF-7, MDA-MB-453, MDA-MB-468 and Capan-1 cells internalized fluorophore-conjugated cystatin C when exposed to physiological concentrations (1 microm). During cystatin C incubation, intracellular cystatin C increased after 5 min and accumulated for at least 6 h, reaching four to six times the baseline level. Western blotting showed that the internalized inhibitor was not degraded. It was functionally intact and extracts of cells exposed to cystatin C showed a higher capacity to inhibit papain and cathepsin B than control cells (decrease in enzyme activity of 34% and 37%, respectively). The uptake of labelled cystatin C was inhibited by unlabelled inhibitor, suggesting a specific pathway for the internalization. We conclude that the cysteine protease inhibitor cystatin C is internalized in significant quantities in various cancer cell lines. This is a potentially important physiological phenomenon not previously described for this group of inhibitors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.