Lipid peroxidation products reduce lysosomal protease activities in human retinal pigment epithelial cells via two different mechanisms of action
In age-related macular degeneration (AMD), reduced lysosomal capacity may contribute to lipofuscinogenesis and progressive dysfunction of the retinal pigment epithelium (RPE). We previously demonstrated that lipid peroxidation-related protein modifications inhibit lysosomal degradation of photorecep...
Gespeichert in:
| Hauptverfasser: | , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
February 2010
|
| In: |
Experimental eye research
Year: 2010, Jahrgang: 90, Heft: 2, Pages: 261-266 |
| ISSN: | 1096-0007 |
| DOI: | 10.1016/j.exer.2009.10.014 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.exer.2009.10.014 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0014483509003170 
|
| Verfasserangaben: | Tim U. Krohne, Elke Kaemmerer, Frank G. Holz, Jürgen Kopitz |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1838211616 | ||
| 003 | DE-627 | ||
| 005 | 20240327080210.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230306s2010 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.exer.2009.10.014 |2 doi | |
| 035 | |a (DE-627)1838211616 | ||
| 035 | |a (DE-599)KXP1838211616 | ||
| 035 | |a (OCoLC)1389821300 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Krohne, Tim Ulrich |d 1974- |e VerfasserIn |0 (DE-588)123782643 |0 (DE-627)706425618 |0 (DE-576)29387638X |4 aut | |
| 245 | 1 | 0 | |a Lipid peroxidation products reduce lysosomal protease activities in human retinal pigment epithelial cells via two different mechanisms of action |c Tim U. Krohne, Elke Kaemmerer, Frank G. Holz, Jürgen Kopitz |
| 264 | 1 | |c February 2010 | |
| 300 | |a 6 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Online verfügbar 4 November 2009 | ||
| 500 | |a Gesehen am 06.03.2023 | ||
| 520 | |a In age-related macular degeneration (AMD), reduced lysosomal capacity may contribute to lipofuscinogenesis and progressive dysfunction of the retinal pigment epithelium (RPE). We previously demonstrated that lipid peroxidation-related protein modifications inhibit lysosomal degradation of photoreceptor outer segment (POS) proteins in RPE cells. Herein, we investigate the effects of lipid peroxidation products on activities of key RPE lysosomal proteases. In lysosomes isolated from primary human RPE cells, lipid peroxidation products 4-hydroxynonenal (HNE) and malondialdehyde (MDA) exerted a dose-dependent inhibitory effect on cysteine proteases cathepsin B and L, with biologically relevant concentrations of 1 μM resulting in a reduction of enzyme activities by 88-94%. This effect was confirmed in cultured RPE cells. Using mass spectrometry, covalent HNE and MDA adducts were detected in the active center region of inactivated cathepsins. POS previously modified with HNE and MDA likewise caused a dose-dependent reduction of cathepsin B and L activities in isolated lysosomes and, in addition, inhibited the aspartic protease cathepsin D. Our results indicate that lipid peroxidation products in vitro interfere with RPE lysosomal protease activities by two different mechanisms of action: (i) HNE and MDA directly inactivate lysosomal cysteine proteases by covalent binding to the active center; (ii) HNE- and MDA-mediated protein modifications convert proteolytic substrates into competitive inhibitors of lysosomal proteases. Via these mechanisms, lipid peroxidation products may induce lysosomal dysfunction and lipofuscinogenesis in the aging RPE and thus contribute to the pathogenesis of AMD. | ||
| 650 | 4 | |a age-related macular degeneration | |
| 650 | 4 | |a cathepsin | |
| 650 | 4 | |a cell culture | |
| 650 | 4 | |a lipid peroxidation | |
| 650 | 4 | |a lysosome | |
| 650 | 4 | |a outer segments | |
| 650 | 4 | |a oxidative stress | |
| 650 | 4 | |a retinal pigment epithelium | |
| 700 | 1 | |a Kämmerer-Gaßler, Elke |d 1980- |e VerfasserIn |0 (DE-588)132226391 |0 (DE-627)519545079 |0 (DE-576)261532251 |4 aut | |
| 700 | 1 | |a Holz, Frank G. |d 1962- |e VerfasserIn |0 (DE-588)114875855 |0 (DE-627)549545182 |0 (DE-576)289811589 |4 aut | |
| 700 | 1 | |a Kopitz, Jürgen |e VerfasserIn |0 (DE-588)1033923397 |0 (DE-627)743674472 |0 (DE-576)16530393X |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Experimental eye research |d Amsterdam [u.a.] : Elsevier, 1962 |g 90(2010), 2 vom: Feb., Seite 261-266 |h Online-Ressource |w (DE-627)266018033 |w (DE-600)1466924-9 |w (DE-576)104193697 |x 1096-0007 |7 nnas |a Lipid peroxidation products reduce lysosomal protease activities in human retinal pigment epithelial cells via two different mechanisms of action |
| 773 | 1 | 8 | |g volume:90 |g year:2010 |g number:2 |g month:02 |g pages:261-266 |g extent:6 |a Lipid peroxidation products reduce lysosomal protease activities in human retinal pigment epithelial cells via two different mechanisms of action |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.exer.2009.10.014 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://www.sciencedirect.com/science/article/pii/S0014483509003170 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20230306 | ||
| 993 | |a Article | ||
| 994 | |a 2010 | ||
| 998 | |g 1033923397 |a Kopitz, Jürgen |m 1033923397:Kopitz, Jürgen |d 910000 |d 912000 |d 50000 |e 910000PK1033923397 |e 912000PK1033923397 |e 50000PK1033923397 |k 0/910000/ |k 1/910000/912000/ |k 0/50000/ |p 4 |y j | ||
| 999 | |a KXP-PPN1838211616 |e 4283639931 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"origin":[{"dateIssuedDisp":"February 2010","dateIssuedKey":"2010"}],"name":{"displayForm":["Tim U. Krohne, Elke Kaemmerer, Frank G. Holz, Jürgen Kopitz"]},"recId":"1838211616","note":["Online verfügbar 4 November 2009","Gesehen am 06.03.2023"],"physDesc":[{"extent":"6 S."}],"id":{"doi":["10.1016/j.exer.2009.10.014"],"eki":["1838211616"]},"type":{"bibl":"article-journal","media":"Online-Ressource"},"title":[{"title_sort":"Lipid peroxidation products reduce lysosomal protease activities in human retinal pigment epithelial cells via two different mechanisms of action","title":"Lipid peroxidation products reduce lysosomal protease activities in human retinal pigment epithelial cells via two different mechanisms of action"}],"relHost":[{"language":["eng"],"physDesc":[{"extent":"Online-Ressource"}],"title":[{"title_sort":"Experimental eye research","title":"Experimental eye research","subtitle":"official journal of the ISER"}],"note":["Gesehen am 18.10.07"],"disp":"Lipid peroxidation products reduce lysosomal protease activities in human retinal pigment epithelial cells via two different mechanisms of actionExperimental eye research","corporate":[{"role":"isb","display":"International Society for Eye Research"}],"type":{"media":"Online-Ressource","bibl":"periodical"},"id":{"zdb":["1466924-9"],"issn":["1096-0007"],"eki":["266018033"]},"part":{"pages":"261-266","issue":"2","text":"90(2010), 2 vom: Feb., Seite 261-266","volume":"90","year":"2010","extent":"6"},"pubHistory":["1.1962 -"],"recId":"266018033","origin":[{"dateIssuedKey":"1962","publisherPlace":"Amsterdam [u.a.] ; London","dateIssuedDisp":"1962-","publisher":"Elsevier ; Academic Press"}]}],"person":[{"given":"Tim Ulrich","family":"Krohne","role":"aut","display":"Krohne, Tim Ulrich"},{"given":"Elke","family":"Kämmerer-Gaßler","role":"aut","display":"Kämmerer-Gaßler, Elke"},{"given":"Frank G.","family":"Holz","role":"aut","display":"Holz, Frank G."},{"given":"Jürgen","family":"Kopitz","role":"aut","display":"Kopitz, Jürgen"}],"language":["eng"]} | ||
| SRT | |a KROHNETIMULIPIDPEROX2010 | ||