ArticleThe Journal of biological chemistry2012
A novel role for α-tocopherol transfer protein (α-TTP) in protecting against chloroquine toxicity.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 25 citations in OpenAlex.
- A TTPA deletion is associated with retinopathy with vitamin E deficiency in the English Cocker Spaniel dog.G3 (Bethesda, Md.) · 2025Article
- Expression of proteins supporting visual function in heterobranch gastropods.Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology · 2025Article
- Increased SEC14L2 expression is associated with clinicopathological features and worse prognosis in oral squamous cell carcinoma.Odontology · 2024Article
- Human Vitamin E deficiency, and what is and is not Vitamin E?Free radical biology & medicine · 2024Review
- Reviving chloroquine for anti-SARS-CoV-2 treatment with cucurbit[7]uril-based supramolecular formulation.Chinese chemical letters = Zhongguo hua xue kuai bao · 2021Article
- Antioxidants in Potatoes: A Functional View on One of the Major Food Crops Worldwide.Molecules (Basel, Switzerland) · 2021Review
- Induction of a 5-lipoxygenase product by daidzein is involved in the regulation of influenza virus replication.Journal of clinical biochemistry and nutrition · 2020Article
- Sphingosine and Sphingosine Kinase 1 Involvement in Endocytic Membrane Trafficking.The Journal of biological chemistry · 2017Article
- Chloroquine and hydroxychloroquine retinopathy-related risk factors in a Turkish cohort.International ophthalmology · 2013Article
- Protective effect of borage seed oil and gamma linolenic acid on DNA: in vivo and in vitro studies.PloS one · 2013Article
- Intracytoplasmic trapping of influenza virus by a lipophilic derivative of aglycoristocetin.Journal of virology · 2012Article
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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