PMID- 10049497
OWN - NLM
STAT- MEDLINE
DCOM- 19990422
LR  - 20131121
IS  - 0003-9861 (Print)
IS  - 0003-9861 (Linking)
VI  - 363
IP  - 1
DP  - 1999 Mar 1
TI  - Glutathione depletion induces giant DNA and high-molecular-weight DNA 
      fragmentation associated with apoptosis through lipid peroxidation and protein 
      kinase C activation in C6 glioma cells.
PG  - 33-42
AB  - Glutathione (GSH) depletion caused by l-buthionine-(S,R)-sulfoximine (BSO) 
      induced apoptosis that was recognized by terminal deoxynucleotidyl 
      transferase-mediated dUTP-biotin nick endo-labeling (TUNEL), nuclear DNA staining 
      with fluorescence dye, and internucleosomal DNA fragmentation in C6 rat glioma 
      cells. The BSO-induced cell death was associated with caspase-3 activation. Lipid 
      peroxidation and protein kinase C (PK-C) activation were observed during the 
      apoptosis of C6 cells, and these events were inhibited by antioxidants and iron 
      chelators without affecting BSO-induced GSH depletion. Furthermore, approximately 
      2 Mbp giant DNA fragments were observed in the BSO-treated cells. The giant DNA 
      fragmentation were followed by approximately 30-700 kbp and then less than 100 
      kbp, including internucleosomal DNA fragmentations. Such serial DNA degradation 
      was prevented by the antioxidants, the iron chelators, and the PK-C inhibitors. 
      These results suggest that during apoptosis induced by GSH-depletion caused by 
      BSO, reactive oxygen species endogenously produced cause lipid peroxidation and 
      that the lipid peroxidation induced PK-C activation, processes which are thought 
      to be involved in the giant DNA, high-molecular-weight DNA, and the 
      internucleosomal DNA fragmentations.
CI  - Copyright 1999 Academic Press.
FAU - Higuchi, Y
AU  - Higuchi Y
AD  - Department of Pharmacology, Kanazawa University School of Medicine, Ishikawa, 
      Kanazawa, 920-8640, Japan.higuchi@kenroku.kanazawa-u.ac.jp
FAU - Matsukawa, S
AU  - Matsukawa S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arch Biochem Biophys
JT  - Archives of biochemistry and biophysics
JID - 0372430
RN  - 0 (Caspase Inhibitors)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Reactive Oxygen Species)
RN  - 1406-18-4 (Vitamin E)
RN  - 5072-26-4 (Buthionine Sulfoximine)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspases)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Buthionine Sulfoximine/pharmacology
MH  - Caspase 3
MH  - Caspase Inhibitors
MH  - Caspases/metabolism
MH  - Cell Death
MH  - DNA/*metabolism
MH  - DNA Fragmentation
MH  - Enzyme Inhibitors/pharmacology
MH  - Glutathione/*deficiency/metabolism
MH  - In Situ Nick-End Labeling
MH  - Intracellular Fluid/metabolism
MH  - Lipid Peroxidation/*physiology
MH  - Protein Kinase C/*metabolism
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
MH  - Tumor Cells, Cultured
MH  - Vitamin E/pharmacology
EDAT- 1999/03/02 00:00
MHDA- 1999/03/02 00:01
CRDT- 1999/03/02 00:00
PHST- 1999/03/02 00:00 [pubmed]
PHST- 1999/03/02 00:01 [medline]
PHST- 1999/03/02 00:00 [entrez]
AID - S0003-9861(98)91067-0 [pii]
AID - 10.1006/abbi.1998.1067 [doi]
PST - ppublish
SO  - Arch Biochem Biophys. 1999 Mar 1;363(1):33-42. doi: 10.1006/abbi.1998.1067.