PMID- 12566072
OWN - NLM
STAT- completed
DA  - 20030204
DCOM- 20030825
LR  - 20040209
IS  - 0891-5849
VI  - 34
IP  - 4
DP  - 2003 Feb 15
TI  - DPI induces mitochondrial superoxide-mediated apoptosis.
PG  - 465-77
AB  - The iodonium compounds diphenyleneiodonium (DPI) and diphenyliodonium
      (IDP) are well-known phagocyte NAD(P)H oxidase inhibitors. However, it has
      been shown that at high concentrations they can inhibit the mitochondrial
      respiratory chain as well. Since inhibition of the mitochondrial
      respiratory chain has been shown to induce superoxide production and
      apoptosis, we investigated the effect of iodonium compounds on
      mitochondria-derived superoxide and apoptosis. Mitochondrial superoxide
      production was measured on both cultured cells and isolated rat-heart
      submitochondrial particles. Mitochondria function was examined by
      monitoring mitochondrial membrane potential. Apoptotic pathways were
      studied by measuring cytochrome c release and caspase 3 activation.
      Apoptosis was characterized by detecting DNA fragmentation on agarose gel
      and measuring propidium iodide- (PI-) stained subdiploid cells using flow
      cytometry. Our results showed that DPI could induce mitochondrial
      superoxide production. The same concentration of DPI induced apoptosis by
      decreasing mitochondrial membrane potential and releasing cytochrome c.
      Addition of antioxidants or overexpression of MnSOD significantly reduced
      DPI-induced mitochondrial damage, cytochrome c release, caspase
      activation, and apoptosis. These observations suggest that DPI can induce
      apoptosis via induction of mitochondrial superoxide. DPI-induced
      mitochondrial superoxide production may prove to be a useful model to
      study the signaling pathways of mitochondrial superoxide.
AD  - Purdue University, Department of Basic Medical Sciences, West Lafayette,
      IN 47907, USA.
FAU - Li, Nianyu
AU  - Li N
FAU - Ragheb, Kathy
AU  - Ragheb K
FAU - Lawler, Gretchen
AU  - Lawler G
FAU - Sturgis, Jennie
AU  - Sturgis J
FAU - Rajwa, Bartek
AU  - Rajwa B
FAU - Melendez, J Andres
AU  - Melendez JA
FAU - Robinson, J Paul
AU  - Robinson JP
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Free Radic Biol Med
JID - 8709159
RN  - 0 (Antioxidants)
RN  - 0 (Cytochrome c Group)
RN  - 0 (Onium Compounds)
RN  - 11062-77-4 (Superoxides)
RN  - 244-54-2 (diphenyleneiodonium)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 3.4.22.- (Caspases)
RN  - EC 3.4.22.- (caspase-3)
SB  - IM
MH  - Animals
MH  - Antioxidants/pharmacology
MH  - Apoptosis/*drug effects
MH  - Caspases/metabolism
MH  - Cytochrome c Group/metabolism
MH  - DNA Fragmentation
MH  - Enzyme Activation/drug effects
MH  - Fibrosarcoma
MH  - Gene Expression
MH  - HL-60 Cells
MH  - Human
MH  - Membrane Potentials/drug effects
MH  - Mitochondria/*drug effects/*metabolism/ultrastructure
MH  - Mitochondria, Heart/ultrastructure
MH  - Myocardium/ultrastructure
MH  - Onium Compounds/*pharmacology
MH  - Rats
MH  - Submitochondrial Particles/metabolism
MH  - Superoxide Dismutase/genetics
MH  - Superoxides/*metabolism/pharmacology
MH  - Tumor Cells, Cultured
EDAT- 2003/02/05 04:00
MHDA- 2003/08/26 05:00
AID - S0891584902013254 [pii]
PST - ppublish
SO  - Free Radic Biol Med 2003 Feb 15;34(4):465-77.