The mitochondrial respiratory complex I is a target for 15-deoxy-delta12,14-prostaglandin J2 action.

Abstract

The prostaglandin J2 derivative 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) is a very active compound with important effects on inflammation, apoptosis, and cell growth processes. To exert this broad range of effects, 15d-PGJ2 binds and alters the activity of diverse proteins, which consequently are postulated to be mediators of its action. Among them are the transcription factors peroxisome proliferator-activated receptor gamma and nuclear factor kappaB, which are thought to play an essential role in the antitumorigenic and anti-inflammatory actions of 15d-PGJ2. Here, we show that 15d-PGJ2, at micromolar concentrations, efficiently blocks state 3 oxygen consumption in intact nonsynaptic mitochondria isolated from rat cerebral cortex. This effect is attributable to the inhibition by this prostaglandin of the activity of the enzyme NADH-ubiquinone reductase (complex I) of the mitochondrial respiratory chain. In addition to this, 15d-PGJ2 dramatically increases the rate of reactive oxygen species generation by complex I. The inhibition by 15d-PGJ2 of complex I activity was abolished by dithiothreitol, which raises the possibility that adduct formation with a critical component of complex I accounts for the inhibitory effect of this prostaglandin. These results clearly identified mitochondrial complex I as a new target for 15d-PGJ2 actions.

• Authors: B Martínez, A Pérez-Castillo, A Santos
• Journal: Journal of lipid research (J Lipid Res) Vol. 46 Issue 4 Pg. 736-43 (Apr 2005) ISSN: 0022-2275 [Print] United States
• PMID: 15654126 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 15-deoxyprostaglandin J2
• Enzyme Inhibitors
• Reactive Oxygen Species
• Electron Transport Complex I
• Prostaglandin D2
• Oxygen

Topics

• Animals
• Electron Transport Complex I (antagonists & inhibitors, metabolism)
• Enzyme Inhibitors (pharmacology)
• Mitochondria (drug effects, metabolism)
• Oxygen (metabolism)
• Oxygen Consumption (drug effects)
• Prostaglandin D2 (analogs & derivatives, metabolism, pharmacology)
• Rats
• Rats, Wistar
• Reactive Oxygen Species (metabolism)