Labieniec 2009 Chem Biol Interact
|Labieniec M, Przygodzki T, Cársky J, Malinska D, Rysz J, Watala C (2009) Effects of resorcylidene aminoguanidine (RAG) on selected parameters of isolated rat liver mitochondria. Chem Biol Interact 179:280-7.|
Abstract: In the present investigation, we attempted to study possible mechanisms of the interactions of resorcylidene aminoguanidine (RAG), the agent with a recognized anti-glycation and antioxidative activity, with rat liver mitochondria. We hypothesized that RAG affects organization of the lipid bilayer in mitochondrial membranes and thus impairs transmembrane Ca2+ redistribution, transmembrane potential, and respiration capacity. Isolated mitochondria were exposed to RAG (50–200 μM) and several parameters of their function monitored employing spectrofluorimetric, cytometric, and respirometric techniques. Mitochondrial membrane potential and membrane fluidity were tracked using the staining with rhodamine 123 (Rh123) and 1,6-diphenyl-1,3,5-hexatriene (DPH), respectively. Mitochondrial respiration and oxidative phosphorylation was monitored with a high-resolution respirometry, and mobilization of Ca2+ was detected using spectrofluorimetry with Calcium Green 5-N. RAG depolarized and fluidized mitochondrial membrane, as deduced from reduced fluorescence of intramitochondrial Rh123 and decreased DPH fluorescence anisotropy. The slight inhibitory effect of 100–200 μM RAG on mitochondrial respiratory capacity was observed merely when monitored in the presence of ADP. The reduced sensitivity of mitochondria to calcium-induced depolarization was significant only at higher RAG concentrations (100–200 μM). Moreover, RAG induced pronounced conformational changes in two model proteins: bovine serum albumin and cytochrome c. These findings indicate that regardless of its depolarizing and fluidizing properties, RAG does not largely affect the mitochondrial respiration, although it may significantly lower oxidative phosphorylation when used at higher concentrations.
• Keywords: (bio)Membranes, Rat liver mitochondria, Resorcylidene aminoguanidine (RAG), Membrane potential, Ca2+ homeostasis, Membrane fluidity
• O2k-Network Lab: PL Lodz Watala C
Organism: Rat Tissue;cell: Liver Preparation: Isolated mitochondria
Regulation: Ion;substrate transport Coupling state: OXPHOS