Biochimica et biophysica acta
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Biochim. Biophys. Acta · Jul 2009
ReviewCardioprotection: a radical view Free radicals in pre and postconditioning.
A series of brief (a few minutes) ischemia/reperfusion cycles (ischemic preconditioning, IP) limits myocardial injury produced by a subsequent prolonged period of coronary artery occlusion and reperfusion. Postconditioning (PostC), which is a series of brief (a few seconds) reperfusion/ischemia cycles at reperfusion onset, attenuates also ischemia/reperfusion injury. In recent years the main idea has been that reactive oxygen species (ROS) play an essential, though double-edged, role in cardioprotection: they may participate in reperfusion injury or may play a role as signaling elements of protection in the pre-ischemic phase. ⋯ Emerging evidence suggests that in a preconditioning scenario a redox signal is required during the first few minutes of myocardial reperfusion following the index ischemic period. Intriguingly, the ROS signaling in the early reperfusion appear crucial to both preconditioning- and postconditioning-induced protection. Therefore, our and others' results suggest that the role of ROS in reperfusion may be reconsidered as they are not only deleterious.
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Biochim. Biophys. Acta · Jun 2009
ReviewMobility and function of coenzyme Q (ubiquinone) in the mitochondrial respiratory chain.
The kinetic analysis by Kröger and Klingenberg on electron transfer in the Coenzyme Q region led to the conclusion that the quinone behaves kinetically as a homogeneous pool freely diffusing in the lipid bilayer, thus setting the basis for the widely accepted random diffusion model of electron transfer. The recent description of supramolecular complexes of the respiratory chain enzymes, in particular Complex I-III supercomplexes, has reopened the problem of electron transfer in the Coenzyme Q region. ⋯ In this review we analyse in detail the reasons that suggested Coenzyme Q pool behaviour; although electron transfer between Complexes I and III indeed appears to be effected by substrate channelling, the Coenzyme Q pool is in equilibrium with bound quinone and is required to fill the site(s) within the supercomplex. In addition, the pool equation of Kröger and Klingenberg still describes in the most adequate way the electron transfer from Complex II and other Coenzyme Q-reducing enzymes to Complex III, besides the energy-dependent reverse electron transfer from Complex II to Complex I.
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Lysosomal diseases are inherited metabolic disorders caused by defects in a wide spectrum of lysosomal and a few non-lysosomal proteins. In most cases a single type of primary storage material is identified, which has been used to name and classify the disorders: hence the terms sphingolipidoses, gangliosidoses, mucopolysaccharidoses, glycoproteinoses, and so forth. ⋯ Lipids - glycosphingolipids and phospholipids, as well as cholesterol - are the most ubiquitous and best studied of these secondary storage materials. While in the past typically considered nonspecific and nonconsequential features of these diseases, newer studies suggest direct links between secondary storage and disease pathogenesis and support the view that understanding all aspects of this sequestration process will provide important insights into the cell biology and treatment of lysosomal disease.
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Biochim. Biophys. Acta · Apr 2009
ReviewTreating lysosomal storage disorders: current practice and future prospects.
There are over 40 human disease states that are caused by defects in various aspects of lysosomal function. Over the past two decades there has been dramatic progress in the development and evaluation of therapies for lysosomal storage disorders, several of which are now in routine clinical use or in clinical trials. The greatest current challenge is in developing effective therapies for treating the CNS manifestations of these complex disorders. In this article, we will review the current therapies/approaches being considered for treating lysosomal storage diseases and give a perspective on the scientific, medical, social and ethical issues they raise.
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Lysosomal storage diseases represent a group of about 50 genetic disorders caused by deficiencies of lysosomal and non-lysosomal proteins. Patients accumulate compounds which are normally degraded in the lysosome. In many diseases this accumulation affects various organs leading to severe symptoms and premature death. ⋯ The spectrum covers e.g. receptor activation by non-physiologic ligands, modulation of receptor response and intracellular effectors of signal transduction cascades, impairment of autophagy, and others. Importantly, many of these processes are associated with accumulation of storage material in non-lysosomal compartments. Here we summarize current knowledge on the effects that storage material can elicit on the cellular level.