Cellular localization of the inhibitory action of abruquinone A against respiratory burst in rat neutrophils

Abstract

1 The possible mechanisms of action of the inhibitory eect of abruquinone A on the respiratory burst in rat neutrophils in vitro was investigated. 2 Abruquinone A caused an irreversible and a concentration-dependent inhibition of formylmethionylleucyl-phenylalanine (fMLP) plus dihydrocytochalasin B (CB)-and phorbol 12-myristate 13-acetate (PMA)-induced superoxide anion (O 2 . 5 Abruquinone A did not aect the enzyme activities of neutrophil cytosolic protein kinase C (PKC) and porcine heart protein kinase A (PKA). 6 Abruquinone A had no eect on intracellular guanosine 3' : 5'-cyclic monophosphate (cyclic GMP) levels but decreased the adenosine 3' : 5'-cyclic monophosphate (cyclic AMP) levels. 7 The cellular formation of phosphatidic acid (PA) and phosphatidylethanol (PEt) induced by fMLP/ CB was inhibited by abruquinone A with IC 50 values of 2.2+0.6 mg ml 71 and 2.5+0.3 mg ml 71 , respectively. Abruquinone A did not inhibit the fMLP/CB-induced protein tyrosine phosphorylation but induced additional phosphotyrosine accumulation on proteins of 73 ± 78 kDa in activated neutrophils. 8 Abruquinone A inhibited both the O 2. 7 generation in PMA-activated neutrophil particulate NADPH oxidase (IC 50 0.6+0.1 mg ml 71) and the iodonitrotetrazolium violet (INT) reduction in arachidonic acid (AA)-activated cell-free system (IC 50 1.5+0.2 mg ml 71 ). 9 Collectively, these results indicate that the inhibition of respiratory burst in rat neutrophils by abruquinone A is mediated partly by the blockade of phospholipase C (PLC) and phospholipase D (PLD) pathways, and by suppressing the function of NADPH oxidase through the interruption of electron transport.

Genistein protects against Aβ25–35 induced apoptosis of PC12 cells through JNK signaling and modulation of Bcl-2 family messengers

“…Cytochrome c—a key constituent of the electron transfer chain in cellular respiration [25]—is normally confined to the inner mitochondrial membrane. When apoptosis signaling causes irreparable mDNA damage, cells hosting these mitochondria show increased release of cytochrome c into their cytosol, suggesting a mechanistic marker for apoptosis [26, 27].…”