Lipid (per) oxidation in mitochondria:an emerging target in the ageing process?

Lipids are essential for physiological processes such as maintaining membrane integrity, providing a source of energy and acting as signalling molecules to control processes including cell proliferation, metabolism, inflammation and apoptosis. Disruption of lipid homeostasis can promote pathological changes that contribute towards biological ageing and age-related diseases. Several age-related diseases have been associated with altered lipid metabolism and an elevation in highly damaging lipid peroxidation products; the latter has been ascribed, at least in part, to mitochondrial dysfunction and elevated ROS formation. In addition, senescent cells, which are known to contribute significantly to age-related pathologies, are also associated with impaired mitochondrial function and changes in lipid metabolism. Therapeutic targeting of dysfunctional mitochondrial and pathological lipid metabolism is an emerging strategy for alleviating their negative impact during ageing and the progression to age-related diseases. Such therapies could include the use of drugs that prevent mitochondrial uncoupling, inhibit inflammatory lipid synthesis, modulate lipid transport or storage, reduce mitochondrial oxidative stress and eliminate senescent cells from tissues. In this review, we provide an overview of lipid structure and function, with emphasis on mitochondrial lipids and their potential for therapeutic targeting during ageing and age-related disease

Oxidation of myofibrillar proteins causes contractile dysfunction in human heart failure

Background: Previous studies in microembolized pig hearts (Eur. Heart. J. 27, 875-881, 2006) demonstrated that augmented intracellular accumulation of reactive oxygen species causes oxidative modifications at the level of the contractile machinery. This study was aimed at investigating the role of myofibrillar protein (MP) oxidation\nitrosylation and the relationship between MP oxidation and contractile impairment in human failing myocardium (NYHA class IV). Methods and Results: As compared to samples from non-failing donor hearts (NF-group, n = 15), left ventricular biopsies from explanted failing hearts (NYHA class IV, HF-group, n = 33) displayed a 2.3 \ub1 0.29- and 2.6 \ub1 0.53-fold increase in actin and tropomyosin (Tm) carbonylation respectively, and a 2.2 \ub1 0.47-fold higher level of high-molecular-mass complexes of Tm due to disulphide cross-bridge formation. MP were also modified by reactive nitrogen species. The extent of S-nitrosylation was 1.3 \ub1 0.15-fold higher in the HF-group. Interesting, actin and Tm carbonylation along with Tm oxidation significantly correlated with both loss of viability (r2 = 0.646, P = 6.16E-12; r2 = 0.453, P = 1.58E-07; r2 = 0.221, P = 0.001, respectively), as indicated by plasma TnI levels and contractile impairment (r2 = 0.599, P = 6.88E-112; r2 = 0.457, P = 1.37E-07; r2 = 0.646, P = 6.16E-12, respectively), as shown by reduced left ventricular ejection fraction (LVEF). Conclusion: This study demonstrates that HF-related oxidative and nitrosative stresses induce covalent changes of MP and that these MP changes play a relevant role in contractile impairment as suggested by the inverse correlation between MP oxidation and LVEF

Remote ischemic preconditioning in cyanosed neonates undergoing cardiopulmonary bypass: a randomized controlled trial.

OBJECTIVE: The myocardial protective effect of remote ischemic preconditioning has been demonstrated in heterogeneous groups of patients undergoing cardiac surgery. No studies have examined this technique in neonates. The present study was performed to examine the remote ischemic preconditioning efficacy in this high-risk patient group. METHODS: A preliminary, randomized, controlled trial was conducted to investigate whether remote ischemic preconditioning in cyanosed neonates undergoing cardiac surgery confers protection against cardiopulmonary bypass. Two groups of neonates undergoing cardiac surgery were recruited for the present study: patients with transposition of the great arteries undergoing the arterial switch procedure and patients with hypoplastic left heart syndrome undergoing the Norwood procedure. The subjects were randomized to the remote ischemic preconditioning or sham control groups. Remote ischemic preconditioning was induced by four 5-minute cycles of lower limb ischemia and reperfusion using a blood pressure cuff. Troponin I and the biomarkers for renal and cerebral injury were measured pre- and postoperatively. RESULTS: A total of 39 neonates were recruited-20 with transposition of the great arteries and 19 with hypoplastic left heart syndrome. Of the 39 neonates, 20 were randomized to remote ischemic preconditioning and 19 to the sham control group. The baseline demographics appeared similar between the randomized groups. The cardiopulmonary bypass and crossclamp times were not significantly different between the 2 groups. The troponin I levels were not significantly different at 6 hours after cardiopulmonary bypass nor were the postoperative inotrope requirements. Markers of renal (neutrophil gelatinase-associated lipocalin) and cerebral injury (S100b, neuron-specific enolase) were not significantly different between the 2 groups. CONCLUSIONS: Our data suggest that remote ischemic preconditioning in hypoxic neonates undergoing cardiopulmonary bypass surgery does not provide myocardial, renal, or neuronal protection. Additional studies are needed to examine the relationships among developmental age, hypoxia, and the molecular mechanisms of ischemic preconditioning

How Techniques of Neutralization Legitimize Norm- and Attitude-Inconsistent Consumer Behavior

In accordance with societal norms and values, consumers readily indicate their positive attitudes towards sustainability. However, they hardly take sustainability into account when engaging in exchange relationships with companies. To shed light on this paradox, this paper investigates whether defense mechanisms and the more specific concept of neutralization techniques can explain the discrepancy between societal norms and actual behavior. A multi-method qualitative research design provides rich insights into consumers' underlying cognitive processes and how they make sense of their attitude-behavior divergences. Drawing on the Ways Model of account-taking, which is advanced to a Cycle Model, the findings illustrate how neutralization strategies are used to legitimize inconsistencies between norm-conforming attitudes and actual behavior. Furthermore, the paper discusses how the repetitive reinforcement of neutralizing patterns and feedback loops between individuals and society are linked to the rise of anomic consumer behavior

Integrative Methods for Studying Cardiac Energetics

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