کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5508661 | 1400394 | 2017 | 29 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The selective Bcl-2 inhibitor venetoclax, a BH3 mimetic, does not dysregulate intracellular Ca2+ signaling
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کلمات کلیدی
BCRIICRABT-199BH3 mimeticsarco/endoplasmic reticulum Ca2+ ATPasevenetoclaxB cell lymphoma-27-aminoactinomycin D7-AADCLLDLBCLIP3RIP3Bcl-2inositol 1,4,5-trisphosphate - inositol 1،4،5-trisphosphateendoplasmic reticulum - شبکه آندوپلاسمی SERCA - قلبDiffuse large B-cell lymphoma - لنفوم سلول B بزرگ سلول بزرگChronic lymphocytic leukemia - لوسمی مزمن لنفوئیدیBcl-2 homology - همولوگ Bcl-2Calcium - کلسیمIP3 receptor - گیرنده IP3B-cell receptor - گیرنده سلول Binositol 1,4,5-trisphosphate receptors - گیرنده های inositol 1،4،5-trisphosphate
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Anti-apoptotic B cell-lymphoma-2 (Bcl-2) proteins are emerging as therapeutic targets in a variety of cancers for precision medicines, like the BH3-mimetic drug venetoclax (ABT-199), which antagonizes the hydrophobic cleft of Bcl-2. However, the impact of venetoclax on intracellular Ca2+ homeostasis and dynamics in cell systems has not been characterized in detail. Here, we show that venetoclax did not affect Ca2+-transport systems from the endoplasmic reticulum (ER) in permeabilized cell systems. Venetoclax (1 μM) did neither trigger Ca2+ release by itself nor affect agonist-induced Ca2+ release in a variety of intact cell models. Among the different cell types, we also studied two Bcl-2-dependent cancer cell models with a varying sensitivity towards venetoclax, namely SU-DHL-4 and OCI-LY-1, both diffuse large B-cell lymphoma cell lines. Acute application of venetoclax did also not dysregulate Ca2+ signaling in these Bcl-2-dependent cancer cells. Moreover, venetoclax-induced cell death was independent of intracellular Ca2+ overload, since Ca2+ buffering using BAPTA-AM did not suppress venetoclax-induced cell death. This study therefore shows that venetoclax does not dysregulate the intracellular Ca2+ homeostasis in a variety of cell types, which may underlie its limited toxicity in human patients. Furthermore, venetoclax-induced cell death in Bcl-2-dependent cancer cells is not mediated by intracellular Ca2+ overload. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1864, Issue 6, June 2017, Pages 968-976
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1864, Issue 6, June 2017, Pages 968-976
نویسندگان
Tamara Vervloessem, Hristina Ivanova, Tomas Luyten, Jan B. Parys, Geert Bultynck,