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The Apparent Organ-...
The Apparent Organ-Specificity of Amyloidogenic ApoA-I Variants Is Linked to Tissue-Specific Extracellular Matrix Components
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- Del Giudice, Rita (författare)
- Lund University,Lunds universitet,Malmö universitet,Biofilms Research Center for Biointerfaces,Institutionen för biomedicinsk vetenskap (BMV),Lund Univ, Dept Expt Med Sci, S-22184 Lund, Sweden.,Medicinsk proteinvetenskap,Forskargrupper vid Lunds universitet,Medical Protein Science,Lund University Research Groups
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- Lindvall, Mikaela (författare)
- Lund Univ, Dept Expt Med Sci, S-22184 Lund, Sweden.,Lund University
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- Nilsson, Oktawia (författare)
- Lund University,Lunds universitet,Medicinsk proteinvetenskap,Forskargrupper vid Lunds universitet,Medical Protein Science,Lund University Research Groups
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- Monti, Daria Maria (författare)
- Univ Napoli Federico II, Dept Chem Sci, Complesso Univ Monte St Angelo, I-80126 Naples, Italy.;Ist Nazl Biostrutture & Biosistemi INBB, I-00136 Rome, Italy.,National Institute Of Biostructures And Biosystems,University of Naples Federico II
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- Lagerstedt, Jens O. (författare)
- Lund University,Lunds universitet,Medicinsk proteinvetenskap,Forskargrupper vid Lunds universitet,Medical Protein Science,Lund University Research Groups
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(creator_code:org_t)
- 2022-12-24
- 2023
- Engelska.
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Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 24:1
- Relaterad länk:
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https://doi.org/10.3...
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https://mau.diva-por... (primary) (Raw object)
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http://dx.doi.org/10... (free)
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https://urn.kb.se/re...
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https://doi.org/10.3...
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https://lup.lub.lu.s...
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Abstract
Ämnesord
Stäng
- Apolipoprotein A-I (ApoA-I) amyloidosis is a rare protein misfolding disease where fibrils of the N-terminal domain of the protein accumulate in several organs, leading to their failure. Although ApoA-I amyloidosis is systemic, the different amyloidogenic variants show a preferential tissue accumulation that appears to correlate with the location of the mutation in the protein sequence and with the local extracellular microenvironment. However, the factors leading to cell/tissues damage, as well as the mechanisms behind the observed organ specificity are mostly unknown. Therefore, we investigated the impact of ApoA-I variants on cell physiology and the mechanisms driving the observed tissue specificity. We focused on four ApoA-I amyloidogenic variants and analyzed their cytotoxicity as well as their ability to alter redox homeostasis in cell lines from different tissues (liver, kidney, heart, skin). Moreover, variant-specific interactions with extracellular matrix (ECM) components were measured by synchrotron radiation circular dichroism and enzyme-linked immunosorbent assay. Data indicated that ApoA-I variants exerted a cytotoxic effect in a time and cell-type-specific manner that seems to be due to protein accumulation in lysosomes. Interestingly, the ApoA-I variants exhibited specific preferential binding to the ECM components, reflecting their tissue accumulation pattern in vivo. While the binding did not to appear to affect protein conformations in solution, extended incubation of the amyloidogenic variants in the presence of different ECM components resulted in different aggregation propensity and aggregation patterns.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- Apolipoprotein A-I
- cytotoxicity
- extracellular matrix components
- amyloidosis
- amyloidosis
- Apolipoprotein A-I
- cytotoxicity
- extracellular matrix components
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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