BGP-15 inhibits caspase-independent programmed cell death in acetaminophen-induced liver injury

Nagy, Gábor and Szarka, András and Lotz, Gábor and Dóczi, Judit and Wunderlich, Lívius and Kiss, András and Jemnitz, Katalin and Veres, Zsuzsa and Bánhegyi, Gábor and Schaff, Zsuzsa and Sümegi, Balázs and Mandl, József (2010) BGP-15 inhibits caspase-independent programmed cell death in acetaminophen-induced liver injury. TOXICOLOGY AND APPLIED PHARMACOLOGY, 243 (1). pp. 96-103. ISSN 0041-008X

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It has been recently shown that acute acetaminophen toxicity results in endoplasmic reticulum redox stress and an increase in cells with apoptotic phenotype in liver. Since activation of effector caspases was absent, the relevance of caspase-independent mechanisms in acetaminophen-induced programmed cell death was investigated. BGP-15, a drug with known protective actions in conditions involving redox imbalance. has been co-administered with a single sublethal dose of acetaminophen. Proapoptotic events and outcome of the injury were investigated. ER redox alterations and early ER-stress-related signaling events induced by acetaminophen, such as ER glutathione depletion. phosphorylation of eIF2 alpha and JNK and induction of the transcription factor GADD153, were not counteracted by co-treatment with BGP-15. However, BGP-15 prevented AIF mitochondria-to-nucleus translocation and mitochondrial depolarization. BGP-15 co-treatment attenuated the rate of acetaminophen-induced cell death as assessed by apoptotic index and enzyme serum release. These results reaffirm that acute acetaminophen toxicity involves oxidative stress-induced caspase-independent cell death. In addition, pharmacological inhibition of AIF translocation may effectively protect against or at least delay acetaminophen-induced programmed cell death. (C) 2009 Elsevier Inc. All rights reserved.

Item Type: Article
Subjects: Q Science / természettudomány > QD Chemistry / kémia
Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3011 Biochemistry / biokémia
R Medicine / orvostudomány > RM Therapeutics. Pharmacology / terápia, gyógyszertan
Depositing User: MTMT SWORD
Date Deposited: 18 Jan 2017 16:36
Last Modified: 18 Jan 2017 16:36

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