RRC ID 17675
著者 Morimoto R, Obinata A.
タイトル Overexpression of hematopoietically expressed homeoprotein induces nonapoptotic cell death in mouse prechondrogenic ATDC5 cells.
ジャーナル Biol Pharm Bull
Abstract Physiological cell death is an essential event in normal development and maintenance of homeostasis. Recently, the morphological and pharmacological characteristics of programmed cell death, which are distinct from those of apoptosis under physiological and pathological conditions, have been reported. However, the molecular mechanism and executioner of this type of cell death are unknown. We show that overexpression of hematopoietically expressed homeoprotein (Hex), a homeoprotein of divergent type, and enhanced green fluorescent protein (EGFP) fusion protein (Hex-EGFP) induces cell death in mouse chondrogenic cell line ATDC5. The expression rate of Hex-EGFP decreased more rapidly than that of EGFP 96 h after transfection. The time-lapse image of living cells revealed the Hex-EGFP-positive cells rapidly died in a necrosis-like fashion. The nuclei of Hex-EGFP-expressing cells were rarely fragmented; however, these cells were negative for terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining. The expression rate of Hex-EGFP clearly increased by treatment with radical scavengers, propyl gallate and butylated hydroxyanisole, slightly increased with a caspase inhibitor, zVAD-fmk, and was not affected by N-acetyl cysteine in ATDC5 cells. A fluorescent probe indicated that reactive oxygen species (ROS) were localized near the nuclei in Hex-EGFP-positive cells. In differentiated ATDC5 cells, as hypertrophic chondrocyte-like cells, the expression rate of Hex-EGFP increased above that in uninduced ATDC5 cells. These results suggest that Hex induces nonapoptotic cell death through local accumulation of reactive oxygen species, and mature chondrocytes, which express Hex, might be able to escape cell death induced by Hex in cartilage.
巻・号 34(10)
ページ 1589-95
公開日 2011-1-1
DOI 10.1248/bpb.34.1589
PII JST.JSTAGE/bpb/34.1589
PMID 21963500
MeSH Acetylcysteine / pharmacology* Amino Acid Chloromethyl Ketones / pharmacology Animals Apoptosis / physiology Cartilage / cytology Cartilage / metabolism Cell Death / physiology* Cell Differentiation Cell Line Cell Nucleus / metabolism Chondrocytes / cytology Chondrocytes / metabolism Chondrogenesis / physiology Cysteine Proteinase Inhibitors / pharmacology Drug Evaluation, Preclinical Free Radical Scavengers / pharmacology Green Fluorescent Proteins / metabolism Heart Function Tests / drug effects Homeodomain Proteins / physiology* Mice Molecular Targeted Therapy Necrosis / metabolism* Reactive Oxygen Species / metabolism Time Factors Transcription Factors / physiology* Transfection Up-Regulation
IF 1.863
引用数 0
WOS 分野 PHARMACOLOGY & PHARMACY
リソース情報
ヒト・動物細胞 ATDC5(RCB0565)