| Online-Ressource |
Verfasst von: | Shichiri, Mototada [VerfasserIn]  |
| Rotzoll, Daisy E. [VerfasserIn]  |
Titel: | A novel role for α-tocopherol transfer protein (α-TTP) in protecting against chloroquine toxicity |
Verf.angabe: | Mototada Shichiri, Nozomu Kono, Yuta Shimanaka, Masaki Tanito, Daisy E. Rotzoll, Yasukazu Yoshida, Yoshihisa Hagihara, Hiroshi Tamai, and Hiroyuki Arai |
Jahr des Originals: | 2011 |
Umfang: | 9 S. |
Fussnoten: | Published, JBC Papers in Press, December 6, 2011 ; Gesehen am 03.08.2018 |
Titel Quelle: | Enthalten in: The journal of biological chemistry |
Jahr Quelle: | 2012 |
Band/Heft Quelle: | 287(2012), 4, S. 2926-2934 |
ISSN Quelle: | 1083-351X |
Abstract: | Chloroquine (CQ) is a widely prescribed anti-malarial agent and is also prescribed to treat autoimmune diseases. Clinical treatment with CQ is often accompanied by serious side effects such as hepatitis and retinopathy. As a weak base, CQ accumulates in intracellular acidic organelles, raises the pH, and induces osmotic swelling and permeabilization of acidic organelles, which account for CQ-induced cytotoxicity. We reported previously that CQ treatment caused α-tocopherol transfer protein (α-TTP), a gene product of familial vitamin E deficiency, to change its location from the cytosol to the surface of acidic organelles. Here we show that α-TTP plays a novel role in protecting against CQ toxicity both in vitro and in vivo. In the presence of CQ, rat hepatoma McARH7777 cells, which do not express α-TTP endogenously, showed more severe cytotoxicity, such as larger vacuolation of acidic organelles and caspase activation, than α-TTP transfectant cells. Similarly, α-TTP knockout mice showed more severe CQ toxicity, such as hepatotoxicity and retinopathy, than wild-type mice. These effects were not ameliorated by vitamin E supplementation. In contrast to bafilomycin A1 treatment, which prevents CQ accumulation in cells by raising the pH of acidic organelles, α-TTP expression prevented CQ accumulation without affecting the pH of acidic organelles. Taken together, our data suggest that α-TTP protects against CQ toxicity by preventing CQ accumulation in acidic organelles through a mechanism distinct from vitamin E transport. |
DOI: | doi:10.1074/jbc.M111.321281 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Kostenfrei: Verlag: http://dx.doi.org/10.1074/jbc.M111.321281 |
| Kostenfrei: Verlag: http://www.jbc.org/content/287/4/2926 |
| DOI: https://doi.org/10.1074/jbc.M111.321281 |
Datenträger: | Online-Ressource |
Sprache: | eng |
K10plus-PPN: | 1578249538 |
Verknüpfungen: | → Zeitschrift |
¬A¬ novel role for α-tocopherol transfer protein (α-TTP) in protecting against chloroquine toxicity / Shichiri, Mototada [VerfasserIn] (Online-Ressource)