Document Detail

Rotenone, a mitochondrial NADH dehydrogenase inhibitor, induces cell surface expression of CD13 and CD38 and apoptosis in HL-60 cells.
MedLine Citation:
PMID:  8833408     Owner:  NLM     Status:  MEDLINE    
We previously demonstrated that the mitochondrial NADH dehydrogenase subunit 2 (ND2) gene was overexpressed in human acute myelogenous leukemia (AML) cells. Since this finding suggested that ND2 gene expression was related to myeloid differentiation, we here investigated the effects of rotenone, a specific NADH dehydrogenase inhibitor, on HL-60 cell growth, differentiation and death. Fifty nM rotenone inhibited the growth of HL-60 cells and caused an increase in the cell population in the G(2) +M phase. In the quantitative comparison of myeloid antigen, the expression of CD13 and CD38 were relatively increased in the rotenone-treated cells. These findings suggest that the inhibition of NADH dehydrogenase changes the cell cycle and induces some specific surface antigens of HL-60 cells. On the other hand, the expression of ND2 gene remained unchanged after the rotenone treatment, suggesting the rotenone-mediated mitochondrial inhibition did not affect the mitochondrial gene expression. Five mu M rotenone strongly inhibited the cellular proliferation. Electron microscopy and an electrophoretic analysis of DNA showed that the majority of the HL-60 cells were induced into typical apoptosis within 24-48 hours. On the basis of this and other studies, we believe that mitochondrial function is directly involved in both cellular differentiation and apoptotic cell death.
T Matsunaga; J Kudo; K Takahashi; K Dohmen; K Hayashida; S Okamura; H Ishibashi; Y Niho
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Leukemia & lymphoma     Volume:  20     ISSN:  1042-8194     ISO Abbreviation:  Leuk. Lymphoma     Publication Date:  1996 Feb 
Date Detail:
Created Date:  1997-06-12     Completed Date:  1997-06-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9007422     Medline TA:  Leuk Lymphoma     Country:  SWITZERLAND    
Other Details:
Languages:  eng     Pagination:  487-94     Citation Subset:  IM    
The First Department of Internal Medicine, Kyushu University, Fukuoka, Japan.
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MeSH Terms
ADP-ribosyl Cyclase
Antigens, CD*
Antigens, CD13 / biosynthesis*,  genetics
Antigens, CD38
Antigens, Differentiation / biosynthesis*,  genetics
Antigens, Neoplasm / biosynthesis*,  genetics
Apoptosis / drug effects*
Enzyme Inhibitors / pharmacology*
G2 Phase / drug effects*
Gene Expression Regulation, Leukemic / drug effects*
HL-60 Cells / drug effects*,  enzymology,  pathology
Membrane Glycoproteins
Mitochondria / drug effects*,  enzymology
N-Glycosyl Hydrolases / biosynthesis*,  genetics
NADH Dehydrogenase / antagonists & inhibitors*
Neoplasm Proteins / biosynthesis,  genetics
Proto-Oncogene Proteins c-bcl-2 / biosynthesis,  genetics
Rotenone / pharmacology*
Tetradecanoylphorbol Acetate / pharmacology
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, Differentiation; 0/Antigens, Neoplasm; 0/Enzyme Inhibitors; 0/Membrane Glycoproteins; 0/Neoplasm Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 16561-29-8/Tetradecanoylphorbol Acetate; 83-79-4/Rotenone; EC Dehydrogenase; EC 3.2.2.-/N-Glycosyl Hydrolases; EC Cyclase; EC, CD38; EC protein, human; EC, CD13

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