Inhibition of the mitochondrial F1F0-ATPase by ligands of the peripheral benzodiazepine receptor
Graphical abstract
PBR-ligand PK-11195 inhibits F1F0-ATPase activity in an OSCP-depender manner, similar to the pro-apoptotic benzodiazepine Bz-423.
Section snippets
Acknowledgment
The present work was supported by NIH Grant AI-47450 to G.D.G.
References and notes (30)
- et al.
Bioorg. Med. Chem.
(2001) - et al.
Bioorg. Med. Chem. Lett.
(2003) - et al.
Chem. Biol.
(2005) - et al.
Biochem. Biophys. Res. Commun.
(2005) - et al.
Biochem. Pharmacol.
(2004) - et al.
Biochem. Pharmacol.
(2004) - et al.
Leuk. Res.
(2002) - et al.
Blood
(2004) - et al.
Blood
(2005) - et al.
Biochem. Pharmacol.
(2005)
Eur. J. Pharmacol.
Biochem. Pharmacol.
Exp. Cell Res.
J. Biol. Chem.
J. Neurochem.
Cited by (45)
Translocator protein (18 kDa) (Tspo) in the retina and implications for ocular diseases
2024, Progress in Retinal and Eye ResearchNatural products and other inhibitors of F<inf>1</inf>F<inf>O</inf> ATP synthase
2020, European Journal of Medicinal ChemistryCitation Excerpt :Two analogs (1002, 1118) that differ by substitutions on the diazepinone ring were reported to manifest comparable activity to Bz-423 [145]. PK11195 inhibits both ATP synthesis (EC50 = 33 μM) and hydrolysis (EC50 = 230 μM) by presumably by binding the OSCP subunit [146,147]. As a consequence, PK11195 alters the mitochondrial integrity and selectively targets Bcl-2 knockdowned in HeLa cells and chronic lymphocytic leukemia (CLL) cells [148,149].
Neuroprotective effect of zolpidem against glutamate-induced toxicity is mediated via the PI3K/Akt pathway and inhibited by PK11195
2018, ToxicologyCitation Excerpt :Typical TSPO ligands, such as PK11195, block pro-apoptotic TSPO activities at physiological concentrations (in the nM and low μM range), in various disease models including excitotoxicity, and exerts considerable beneficial effects on neuronal viability (Parker et al., 2002; Rupprecht et al., 2010; Li et al., 2015). More recently, it has been suggested that cellular responses observed with μM concentrations of PK11195, which were initially attributed to the modulation of TSPO function, result from the inhibition of mitochondrial F0F1-ATPase activity (Cleary et al., 2007). As pro-survival zolpidem activity was inhibited by high μM concentration of PK11195, it is possible that zolpidem effects in P19 neurons include those involving the F0F1-ATP synthase.
Forty years later: Mitochondria as therapeutic targets in muscle diseases
2016, Pharmacological ResearchMitochondrial translocator protein (TSPO): From physiology to cardioprotection
2016, Biochemical PharmacologyAn automated phenotype-based microscopy screen to identify pro-longevity interventions acting through mitochondria in C. elegans
2015, Biochimica et Biophysica Acta - Bioenergetics
- †
These authors contributed equally to this work.