Abstract：
:Transient receptor potential melastatin 2 (TRPM2) is an oxidative stress-sensitive Ca2+-permeable channel. The activation of TRPM2 by H2O2 causes cell death in various types of cells. 5-Fluorouracil (5-FU) is an important anticancer drug, but myelosuppression is one of the most frequent adverse effects. The involvement of oxidative stress in 5-FU-induced myelosuppression has been reported, and bone marrow cells are known to express TRPM2. The aim of this study was to investigate whether TRPM2 is involved in 5-FU-induced myelosuppression. Enhancement of H2O2-induced intracellular Ca2+ concentration ([Ca2+]i) increase by 5-FU treatment was observed in human embryonic kidney 293 (HEK) cells stably expressing TRPM2 but not in HEK cells, indicating that 5-FU stimulates TRPM2 activation. In CD117 positive cells from wild type (WT) mouse bone marrow, 5-FU also enhanced the H2O2-induced [Ca2+]i increases, but not in cells from Trpm2 knockout (KO) mice. In the CFU-GM colony assay, the 5-FU-induced reduction of colony number was alleviated by Trpm2 deficiency. Moreover, the reduction of leukocytes in blood by administration with 5-FU in WT mice was also alleviated in Trpm2 KO mice. The activation of TRPM2 in bone marrow cells seems to be involved in 5-FU-induced myelosuppression.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Ishibashi M,Ishii M,Yamamoto S,Mori Y,Shimizu Sdoi
10.1016/j.ejphar.2020.173671subject
Has Abstractpub_date
2021-01-15 00:00:00pages
173671eissn
0014-2999issn
1879-0712pii
S0014-2999(20)30763-9journal_volume
891pub_type
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
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abstract：:The presence of P2X purinoceptors in human umbilical vessels were studied with organ bath recording, radioligand binding assays, autoradiography, and immunohistochemistry. In isolated umbilical arteries and veins from normal term pregnancy, both ATP and alpha,beta-methylene ATP caused concentration-dependent contracti...
journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：1998-07-17 00:00:00
