Title: | Increased human dermal microvascular endothelial cell survival induced by cysteamine |
Author(s): | Besouw, M.; Heuvel, L.P. van den ; Eijsden, R. van; Bongaers, I.; Kluijtmans, L.A. ; Dewerchin, M.; Levtchenko, E.N. |
Publication year: | 2013 |
Source: | Journal of Inherited Metabolic Disease, vol. 36, iss. 6, (2013), pp. 1073-1077 |
ISSN: | 0141-8955 |
DOI: | https://doi.org/10.1007/s10545-013-9588-0 |
Publication type: | Article / Letter to editor |
Please use this identifier to cite or link to this item : https://hdl.handle.net/2066/125972 ![]() |
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Subject: | IGMD 3: Genomic disorders and inherited multi-system disorders IGMD 3: Genomic disorders and inherited multi-system disorders NCMLS 4: Energy and redox metabolism IGMD 8: Mitochondrial medicine NCMLS 4: Energy and redox metabolism IGMD 9: Renal disorder NCMLS 4: Energy and redox metabolism IGMD 9: Renal disorder NCMLS 5: Membrane transport and intracellular motility IGMD 8: Mitochondrial medicine NCMLS 4: Energy and redox metabolism IGMD 9: Renal disorder NCMLS 5: Membrane transport and intracellular motility Tijdelijke code tbv inlezen publicaties Radboudumc - Alleen voor gebruik door Radboudumc |
Organization: | Paediatrics - OUD tm 2017 Laboratory of Genetic, Endocrine and Metabolic Diseases |
Journal title: |
Journal of Inherited Metabolic Disease
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Volume: | vol. 36 |
Issue: | iss. 6 |
Page start: | p. 1073 |
Page end: | p. 1077 |
Abstract: |
BACKGROUND: Cystinosis is an autosomal recessive disease caused by intralysosomal cystine accumulation, treated with cysteamine. Recently, new adverse effects of cysteamine were reported. Skin biopsies showed microvascular proliferation (angioendotheliomatosis). To examine the mechanism of angioendotheliomatosis associated with cysteamine toxicity, we examined the effect of cysteamine on human dermal microvascular endothelial cells (HDMVEC). METHODS: After cysteamine exposure (range 0-3.0 mM) during 24 h, cell viability was measured using water soluble tetrazolium salt-1 (WST-1) in both control HDMVEC and fibroblasts. Cell proliferation and apoptosis rate were measured in HDMVEC by bromodeoxyuridine (BrdU) incorporation and caspase 3 and caspase 7 activity, respectively. Intracellular glutathione (GSH) was measured in HDMVEC after cysteamine exposure of 0, 0.1 or 1.0 mM. Medium and cysteamine were refreshed every 6 h to mimic the in vivo situation. Next, cell viability in HDMVEC was measured after 24 h of GSH exposure (range 0-10.0 mM). RESULTS: HDMVEC viability and proliferation increased after cysteamine exposure 0.03-3.0 mM (p < 0.01) and 0.03-1.0 mM (p = 0.01) respectively; cell viability in fibroblasts was not affected by incubation with cysteamine. Apoptosis remained unaffected by incubation with 0-1.0 mM cysteamine, 3.0 mM caused increased apoptosis. Intracellular GSH was significantly increased after incubation with cysteamine 0.1 mM (p = 0.02) and 1.0 mM (p < 0.01). HDMVEC viability increased after exposure to GSH 1.0-5.0 mM (p < 0.01). CONCLUSION: Cysteamine concentrations, similar to those described in plasma of cystinosis patients, stimulate HDMVEC viability and proliferation and increase intracellular GSH content. We postulate that this mechanism might underlie angioendotheliomatosis induced by cysteamine.
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