Aspirin Induces Mitochondrial Ca2+ Remodeling in Tumor Cells via ROS‒Depolarization‒Voltage-Gated Ca2+ Entry
| العنوان: | Aspirin Induces Mitochondrial Ca2+ Remodeling in Tumor Cells via ROS‒Depolarization‒Voltage-Gated Ca2+ Entry |
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| المؤلفون: | Yoshihiro Suzuki-Karasaki, Toyoko Ochiai, Itsuho Fujikawa, Manami Suzuki-Karasaki, Miki Suzuki-Karasaki, Takashi Ando |
| المصدر: | International Journal of Molecular Sciences Volume 21 Issue 13 International Journal of Molecular Sciences, Vol 21, Iss 4771, p 4771 (2020) |
| بيانات النشر: | MDPI, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Programmed cell death, Calcium Channels, L-Type, voltage-gated Ca2+ entry, Cell Survival, Mitochondrion, Catalysis, Article, lcsh:Chemistry, Inorganic Chemistry, salicylate, depolarization, Cell Line, Tumor, l-type Ca2+ channel, melanoma, Humans, Channel blocker, Physical and Theoretical Chemistry, lcsh:QH301-705.5, Molecular Biology, Spectroscopy, chemistry.chemical_classification, Membrane potential, Reactive oxygen species, Voltage-gated ion channel, Aspirin, Organic Chemistry, Anti-Inflammatory Agents, Non-Steroidal, apoptosis, Depolarization, General Medicine, Computer Science Applications, Cell biology, Mitochondria, lcsh:Biology (General), lcsh:QD1-999, chemistry, Apoptosis, Calcium, Drug Screening Assays, Antitumor |
| الوصف: | Aspirin (acetylsalicylic acid) and its metabolite salicylate, have an anti-melanoma effect by evoking mitochondrial dysfunction through poorly understood mechanisms. Depolarization of the plasma membrane potential leads to voltage-gated Ca2+ entry (VGCE) and caspase-3 activation. In the present study, we investigated the role of depolarization and VGCE in aspirin&rsquo s anti-melanoma effect. Aspirin and to a lesser extent, salicylate (&ge 2.5 mM) induced a rapid (within seconds) depolarization, while they caused comparable levels of depolarization with a lag of 2~4 h. Reactive oxygen species (ROS) generation also occurred in the two-time points, and antioxidants abolished the early ROS generation and depolarization. At the same concentrations, the two drugs induced apoptotic and necrotic cell death in a caspase-independent manner, and antioxidants and Ca2+ channel blockers prevented cell death. Besides ROS generation, reduced mitochondrial Ca2+ (Ca2+m) and mitochondrial membrane potential preceded cell death. Moreover, the cells expressed the Cav1.2 isoform of l-type Ca2+ channel, and knockdown of Cav1.2 abolished the decrease in Ca2+m. Our findings suggest that aspirin and salicylate induce Ca2+m remodeling, mitochondrial dysfunction, and cell death via ROS-dependent depolarization and VGCE activation. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1422-0067 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d09f740597e5ae6c0cbc2a3e8ca9b120Test http://europepmc.org/articles/PMC7370041Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d09f740597e5ae6c0cbc2a3e8ca9b120 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 |
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