MDR1 up-regulated by apoptotic stimuli suppresses apoptotic signaling

Recently, MDR1 (P-glycoprotein) and related transporters have been suggested to play a fundamental role in regulating apoptosis, but little information is available concerning the role of MDR1. Here, the effect of apoptotic stimuli on the MDR1 mRNA and apoptotic signaling was examined in MDR1-overex...

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Published in:Pharmaceutical research 2002-09, Vol.19 (9), p.1323-1329
Main Authors: SAKAEDA, Toshiyuki, NAKAMURA, Tsutomu, SHIRAKAWA, Toshiro, GOTOH, Akinobu, MATSUO, Masafumi, OKUMURA, Katsuhiko, HIRAI, Midori, KIMURA, Takashi, WADA, Atsushi, YAGAMI, Tatsurou, KOBAYASHI, Hironao, NAGATA, Shunji, OKAMURA, Noboru, YOSHIKAWA, Takayoshi
Format: Article
Language:English
Subjects:
Antineoplastic agents
Apoptosis
Apoptosis - drug effects
Apoptosis - physiology
ATP Binding Cassette Transporter, Subfamily B, Member 1 - biosynthesis
ATP Binding Cassette Transporter, Subfamily B, Member 1 - physiology
Biological and medical sciences
Caspase 3
Caspases - biosynthesis
Cell death
Cisplatin - pharmacology
Enzymes
General aspects
Glycoproteins
HeLa Cells
Humans
Medical sciences
Pharmacology. Drug treatments
Polymerase chain reaction
Proteins
Proto-Oncogene Proteins c-bcl-2 - biosynthesis
RNA, Messenger - biosynthesis
Signal Transduction - drug effects
Signal Transduction - physiology
Stem cells
Up-Regulation - drug effects
Up-Regulation - physiology
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Summary:Recently, MDR1 (P-glycoprotein) and related transporters have been suggested to play a fundamental role in regulating apoptosis, but little information is available concerning the role of MDR1. Here, the effect of apoptotic stimuli on the MDR1 mRNA and apoptotic signaling was examined in MDR1-overexpressing cells. The expression levels of mRNA for MDR1, MRP1, MRP2, p53, p21, Bax, and Bcl-2 were measured by real time quantitative polymerase chain reaction in HeLa and its MDR1-overexpressing sublines. The effects of apoptotic stimuli by cisplatin (CDDP) on their levels were also assessed as well as on caspase 3, 8, and 9 activities. MDR1 was rapidly upregulated when the cells were exposed to apoptotic stimuli by CDDP. The increase in Bax mRNA to Bcl-2 mRNA ratio after treatment with CDDP was suppressed in MDR1-overexpressing cells. The increases in caspase 3 and 9 activities after treatment with CDDP were suppressed in MDR1-overexpression cells. MDR1 is upregulated by apoptotic stimuli suppressed apoptotic signaling presumably via the mitochondrial pathway.
ISSN:0724-8741
1573-904X
DOI:10.1023/a:1020302825511