Brown adipose tissue (BAT) physiology and imaging have recently attracted considerable attention. BAT is characterized both by enhanced perfusio
n and increased mitochondrial activity. 99mTc-sestamibi is a lipophilic cationic
tracer that concentrates in mitochondria. Data on the accumulation of 99mTc-sestamibi in BAT are currently lacking. This study investigates the
in vivo99mTc-sestamibi uptake in rat BAT. 99mTc-sestamibi was administered in male Wistar rats of various age and body size. 99mTc-sestamibi uptake was measured in vitro in BAT and white fat (WF) together with cytochrome c oxidase activity. Both 99mTc-sestamibi uptake and cytochrome c oxidase activity were higher in BAT than in WF (P<0.05). 99m
Tc-Sestamibi uptake in both BAT and WF was negatively related to body weight (r= -0.96 and -0.89, respectively) as was the BAT/WF uptake ratio (r = -0.85). These data show a higher 99mTc-sestamibi uptake in
BAT compared to WF, in agreement with the high mitochondrial content and respiratory activity of the former. The strong negative correlation between 99mTc-sestamibi uptake in BAT and body weight (negative allometry), is in accordance to increased needs of thermogenesis in smaller animals. Implications of increased 99mTc-sestamibi uptake in BAT in radionuclide imaging are also discussed.
A 2×2 factorial design was used to evaluate possible preservation
of mitochondrial functions in two cardioprotective experimental models, remote ischemic preconditioning and streptozotocin-induced diabetes mellitus, and their interaction during ischemia/reperfusion injury (I/R) of the heart. Male Wistar rats were randomly allocated into four groups: control (C), streptozotocin-induced diabetic (DM), preconditioned
(RPC) and preconditioned streptozotocin-induced diabetic (DM+RPC).
RPC was conducted by 3 cycles of 5-min hind-limb ischemia and 5-min reperfusion. DM was induced by a single dose of 65mg/kg streptozotocin. Isolated hearts were exposed to ischemia/reperfusion test according to Langendorff. Thereafter mitochondria were isolated and the mitochondrial respiration was measured. Additionally, the ATP synthase activity measurements on the same preparations were done. Animals of all groups subjected to I/Rexhibited a decreased state 3 respiration with the least change noted in DM+RPC group associated with no significant changes in state 2 respiration. In RPC, DM and DM+RPC group, no significant
changes in the activity of ATP synthase were observed after I/R
injury. These results suggest that the endogenous protective mechanisms of RPC and DM do preserve the mitochondrial function in heart when they act in combination.
This review is focused on the unusual composition of the endolymph of the inner ear and its function in mechanoelectrical transduction. The role of K+ and Ca2+ in excitatory influx, the very low Na+, Ca2+ and Mg2+ concentrations of endolymph, stereocilia structure of hair cells and some proteins involved in mechanosensory signal transduction with emphasis on auditory receptors are presented and analyzed in more details. An alternative hypothetical model of ciliary structure and endolymph with a ‘normal’ composition is discussed. It is concluded that the unique endolymph cation content is more than an energy saving mechanism that avoids disturbing circulatory vibrations to achieve a much better mechanosensory resolution. It is the only possible way to fulfil the requirements for a precise ciliary mechanoelectrical transduction in conditions where pressure events with quite diverse amplitudes and duration are transformed into adequate hair cell membrane depolarizations, which are regulated by a sensitive Ca2+-dependent feedback tuning., H. Gagov, M. Chichova, M. Mladenov., and Seznam literatury
Cell-mediated immunity (CMI) response of healthy humans and cancer (Ca) patients to specific tumor antigen and nonspecific (LDV -- lactate dehydrogenase virus) antigen, and of acute myocardial infarction (AMI) and schizophrenia (Sch) patients to nonspecific antigen was investigated. Large differences of CMI response of healthy humans in comparison with Ca, AMI, Sch patients were found. CMI response to antigens displays transferred information about cells under immune surveillance. LDV disturbs the oxidative energy production system. We assume that CMI response to LDV antigen monitors pathological states of mitochondrial energy production which results in disturbances of electromagnetic activity of living cells.
Instead of a comprehensive review, we describe the basic undisputed facts and a modest contribution of our group to the fascinating area of the research on mitochondrial uncoupling proteins. After defining the terms uncoupling, leak, protein-mediated uncoupling, we discuss the assumption that due to their low abundance the novel mitochondrial
uncoupling proteins (UCP2 to UCP5) can provide only a mild uncoupling, i.e. can decrease the proton motive force by several mV only. Contrary to this, the highly thermogenic role of UCP1 in brown adipose tissue is not given only by its high content (~5 % of mitochondrial proteins) but also by the low ATP synthase content and high capacity respiratory chain. Fatty acid cycling mechanism as a plausible explanation for the protonophoretic function of all UCPs and some other mitochondrial carriers is described together with th
e experiments supporting it. The phylogenesis of all UCPs, estimated UCP2 content in several tissues, and details of UCP2 activation are described on the basis of our experiments. Functional activation of UCP2 is proposed to decrease reactive oxygen species (ROS) production. Moreover, reaction
products of lipoperoxidation such as cleaved hydroperoxy-fatty acids and hydroxy-fatty acid can activate UCP2 and promote feedback down-regulation of mitochondrial ROS production.
Aging is a multifactorial process influenced by genetic factors, nutrition, and lifestyle. According to mitochondrial theory of aging, mitochondrial dysfunction is widely considered a major contributor to age-related processes. Mitochondria are both the main source and targets of detrimental reactions initiated in association with age-dependent deterioration of the cellular functions. Reactions leading to increased reactive oxygen species generation, mtDNA mutations, and oxidation of mitochondrial proteins result in subsequent induction of apoptotic events,
impaired oxidative phosphorylation capacity, mitochondrial dynamics, biogenesis and autophagy. This review summarizes the major changes of mitochondria related to aging, with emphasis on mitochondrial DNA mutations, the role of the reactive oxygen species, and structural and functional changes of mitochondria.
Cytochrome c oxidase (COX), the terminal enzyme of mitochondrial electron transport chain, couples electron transport to oxygen with generation of proton gradient indispensable for the production of vast majority of ATP molecules in mammalian cells. The review summarizes current knowledge of COX structure and function of nuclear-encoded COX subunits, which may modulate enzyme activity according to various conditions. Moreover, some nuclear-encoded subunits possess tissue-specific and development-specific isoforms, possibly enabling fine-tuning of COX function in individual tissues. The importance of nuclearencoded subunits is emphasized by recently discovered pathogenic mutations in patients with severe mitopathies. In addition, proteins substoichiometrically associated with COX were found to contribute to COX activity regulation and stabilization of the respiratory supercomplexes. Based on the summarized data, a model of three levels of quaternary COX structure is postulated. Individual structural levels correspond to subunits of the i) catalytic center, ii) nuclear-encoded stoichiometric subunits and iii) associated proteins, which may constitute several forms of COX with varying composition and differentially regulated function.