Heart resistance against stress-induced damages

Activation of peripheral-opioid receptors diminished stress-induced heart damage whereas stimulation of central-opioid receptors enhanced it. Peripheral-opioid receptors do not take part in pathogenesis of the "stress cardiomyopathy". The prostanoid system and processes of lipid peroxidation participate in realisation of cardioprotective effects associated with peripheral-opioid receptors.     

Ribosome‐associated pentatricopeptide repeat proteins function as translational activators in mitochondria of trypanosomes

Mitochondrial ribosomes of Trypanosoma brucei are composed of 9S and 12S rRNAs, eubacterial‐type ribosomal proteins, polypeptides lacking discernible motifs and approximately 20 pentatricopeptide repeat (PPR) RNA binding proteins. Several PPRs also populate the polyadenylation complex; among these, KPAF1 and KPAF2 function as general mRNA 3′ adenylation/uridylation factors. The A/U‐tail enables mRNA binding to the small ribosomal subunit and is essential for translation. The presence of A/U‐tail also correlates with requirement for translation of certain mRNAs in mammalian and insect parasite stages. Here, we inquired whether additional PPRs activate translation of individual mRNAs. Proteomic analysis identified KRIPP1 and KRIPP8 as components of the small ribosomal subunit in mammalian and insect forms, but also revealed their association with the polyadenylation complex in the latter. RNAi knockdowns demonstrated essential functions of KRIPP1 and KRIPP8 in the actively respiring insect stage, but not in the mammalian stage. In the KRIPP1 knockdown, A/U‐tailed mRNA encoding cytochrome c oxidase subunit 1 declined concomitantly with the de novo synthesis of this subunit whereas polyadenylation and translation of cyb mRNA were unaffected. In contrast, the KRIPP8 knockdown inhibited A/U‐tailing and translation of both CO1 and cyb mRNAs. Our findings indicate that ribosome‐associated PPRs may selectively activate mRNAs for translation.     

Role of cannabinoid receptors in regulation of cardiac tolerance to ischemia and reperfusion

Coronary artery occlusion (45 min) and reperfusion (2 h) were modeled in vivo in anesthetized artificially ventilated Wistar rats. Total ischemia (45 min) and reperfusion (30 min) of the isolated rat heart were performed in vitro. The selective agonist of cannabinoid (CB) receptors HU-210 was injected intravenously at a dose of 0.1 mg/kg 15 min prior to the coronary artery ligation. The selective CB1 antagonist SR141716A and the selective CB2 antagonist SR144528 were injected intravenously 25 min prior to ischemia. In vitro, HU-210 and SR141716A were added to the perfusion solution at the final concentrations of 0.1 μM prior to total ischemia. Preliminary injection of HU-210 reduced the infarct size-to-area at risk (IS/AAR) ratio in vivo. This cardioprotective effect was completely abolished by SR141716A but remained after SR144528 injection. Both antagonists had no effect on the IS/AAR ratio. Preliminary injection of the K_ATP channel blocker glibenclamide did not abolish the cardioprotective effect of HU-210. The addition of HU-210 prior to ischemia reduced the creatine phosphokinase (CPK) level in the coronary effluent and decreased left ventricular developed pressure. SR141716A alone had no effect on cardiac contractility and CPK levels. These results suggest that cardiac CB1 receptor activation increases cardiac tolerance to ischemia-reperfusion and has a negative effect on the cardiac pump function. Endogenous cannabinoids are not involved in the regulation of cardiac contractility and tolerance to ischemia and reperfusion. ATP-sensitive k_ATP-channels are not involved in the mechanism of the cardioprotective effect of HU-210.     

Synthesis of cationic lipid transfection agents with <Emphasis Type="Italic">O,O</Emphasis>- or <Emphasis Type="Italic">N,O</Emphasis>-acetal linkages

A synthesis of cationic lipids on the basis of 1,2-di-O-tetradecylglycerol is described. The cationic groups represented by the residues of nitrogenated heterocyclic bases attached to the diglyceride backbone through O,O- and N,O-acetal linkages. The resulting lipids can be used as nonviral delivery systems of genes into eukaryotic cells.     

Effects of activation of μ-, κ<Subscript>1</Subscript>-, δ<Subscript>1</Subscript>-, δ<Subscript>2</Subscript>-, and ORL<Subscript>1</Subscript>-receptors on heart resistance to the pathogenic action of delayed ischemia and reperfusion

Different subtypes of opioid receptors (OR) were activated in rats in vivo to study the activation effect on the heart’s resistance to ischemia and reperfusion. It has been established that administration of deltorphin II, a selective δ₂-OR agonist, lowered the infarct size/area at risk index (IS/AAR) by 23%. Naltrexone, naloxone methiodide (an OR inhibitor not penetrating the blood-brain barrier (BBB)), and naltriben (δ₂-antagonist) eliminated the cardioprotective effect of deltorphin II, while BNTX (a δ₁-antagonist) produced no effect on the cardioprotective action of the δ₂-agonist. The infarct-reducing effect of deltorphin II was eliminated by administration of chelerythrine (a protein kinase C (PKC) inhibitor), glibenclamide (a K_ATP-channels inhibitor), and 5-hydroxydecanoate (a mitochondrial K_ATP-channel blocker). Administration of other opioids did not reduce the IS/AAR index. It has been established that all the deltorphins manifest antiarrhythmic potency. Other opioids do not produce any effect on the incidence of arrhythmia occurrences. The antiarrhythmic effect of deltorphin II was eliminated by preliminary administration of naltrexone, naloxone methiodide, and naltriben, but BNTX did not affect the δ₂-agonist’s anti-arrhythmic effect. The preliminary administration of chelerythrine, a PKC inhibitor, eliminated the δ₂ agonist’s antiarrhythmic action. However, glibenclamide and 5-hydroxydecanoate did not alter the antiarrhythmic effect by deltorphin II. Therefore, activation of the peripheral δ₂-ORs reduces the infarct size and prevents the onset of arrhythmias. The antiarrhythmic effect of the δ₂-OR stimulation is mediated by activating PKC and opening the mitochondrial K_ATP-channels. PKC participates in the antiarrhythmic effect of the δ₂-OR activation, but this effect does not depend on the condition of K_ATP-channels.     

Polycationic amphiphiles based on triethylenetetramine and their transfection efficacy

Novel polycationic amphiphiles derived from triethylenetetramine, a spermine analogue, containing cholesterol or dialkylglycerol residues as hydrophilic domains were synthesized. The amphiphiles and a helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine) served for the preparation of cationic liposomes, physicochemical properties of which were evaluated. A comparative study of cytotoxicity and transfection efficiency demonstrated that the replacement of spermine by triethylenetetramine decreased transfection activity of cationic liposomes.