High surface energy enhances cell response to titanium substrate microstructure

Titanium (Ti) is used for implantable devices because of its biocompatible oxide surface layer. TiO2 surfaces that have a complex microtopography increase bone-to-implant contact and removal torque forces in vivo and induce osteoblast differentiation in vitro. Studies examining osteoblast response to controlled surface chemistries indicate that hydrophilic surfaces are osteogenic, but TiO2 surfaces produced until now exhibit low surface energy because of adsorbed hydrocarbons and carbonates from the ambient atmosphere or roughness induced hydrophobicity. Novel hydroxylated/hydrated Ti surfaces were used to retain high surface energy of TiO2. Osteoblasts grown on this modified surface exhibited a more differentiated phenotype characterized by increased alkaline phosphatase activity and osteocalcin and generated an osteogenic microenvironment through higher production of PGE2 and TGF-beta1. Moreover, 1alpha,25OH2D3 increased these effects in a manner that was synergistic with high surface energy. This suggests that increased bone formation observed on modified Ti surfaces in vivo is due in part to stimulatory effects of high surface energy on osteoblasts.     

Molecular regulation of interferon antiviral response in fish

Interferon (IFN) response is the first line of host defense against virus infection. The recent years have witnessed tremendous progress in understanding of fish IFN antiviral response. Varied number of IFN genes has been identified in different fish species but obviously, they do not show a one-to-one orthologous relationship with mammalian IFN homologs. These genes are divided into two groups with different abilities to induce downstream gene expression through binding to different receptor complexes. Consistently, some fish IFN-stimulated genes such as Mx and PKR have been confirmed for their antiviral effects. In this review, we focus on how fish cells respond to IFNs and how fish IFNs are triggered through TLR pathway and RLR pathway. We highlight the roles of IRF3 and IRF7 in activation of fish IFN response. In addition, the unique mechanisms underlying IRF3/7-dependent fish IFN response and auto-regulation of fish IFN gene expression are discussed.     

Effect of nadcin on energy supply system and apoptosis in ischemia-reperfusion injury to the myocardium

Nadcin in a dose of 90 mg/kg administered to dogs with subacute stage of ischemia-reperfusion myocardial injury immediately after blood flow resumption normalized redox potential of cardiomyocytes and mitochondria and restored the total content of adenyl and pyridine nucleotides. The decrease in the synthesis of ATP and pyridine nucleotides and reduction of the redox potential of the energy supply system were inversely related to the increase in poly-(ADP-ribose)-polymerase activity in the ischemic area and nonischemic region. Nadcin abolished the increase in poly-(ADP-ribose)-polymerase activity in the ischemic area of the right ventricle, nonischemic region, and ischemic area of the left ventricle (by 2.4, 2.9, and 1.52 times, respectively) and normalized bioenergetic activity of cardiomyocytes during ischemia-reperfusion myocardial injury. Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 146, No. 9, pp. 297–300, September, 2008     

Cardiac system bioenergetics: metabolic basis of the Frank-Starling law

The fundamental principle of cardiac behaviour is described by the Frank-Starling law relating force of contraction during systole with end-diastolic volume. While both work and respiration rates increase linearly with imposed load, the basis of mechano-energetic coupling in heart muscle has remained a long-standing enigma. Here, we highlight advances made in understanding of complex cellular and molecular mechanisms that orchestrate coupling of mitochondrial oxidative phosphorylation with ATP utilization for muscle contraction. Cardiac system bioenergetics critically depends on an interrelated metabolic infrastructure regulating mitochondrial respiration and energy fluxes throughout cellular compartments. The data reviewed indicate the significance of two interrelated systems regulating mitochondrial respiration and energy fluxes in cells: (1) the creatine kinase, adenylate kinase and glycolytic pathways that communicate flux changes generated by cellular ATPases within structurally organized enzymatic modules and networks; and (2) a secondary system based on mitochondrial participation in cellular calcium cycle, which adjusts substrate oxidation and energy-transducing processes to meet increasing cellular energy demands. By conveying energetic signals to metabolic sensors, coupled phosphotransfer reactions provide a high-fidelity regulation of the excitation–contraction cycle. Such integration of energetics with calcium signalling systems provides the basis for 'metabolic pacing', synchronizing the cellular electrical and mechanical activities with energy supply processes.     

The energy supply systems in the heart valve leaflet cells during kryopreservation and storage

The condition of animal heart valve allografts after kryopreservation and storage is assessed. After 2-day storage of preparations at 4°C tissue ATP content decreases by 1.5–2 times and remains at this level for 5 days. Freezing of tissues without kryoprotector results in more than 10-fold drop in ATP content and a 2-fold decrease in the total content of pyridine nucleotides. After kryopreservation these parameters decrease by 1.2–1.4 times. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 6, pp. 631–633, June, 1998     

Effect of substrate supply and beta-adrenergic blockade on heart glycogen and triglyceride utilization during exercise in the rat

Summary Exercise-induced heart glycogen and triglyceride mobilization was studied in control rats, in rats with reduced blood glucose supply (fasted rats), in rats with reduced plasma free fatty acids (FFA) supply (nicotinic acid-treated rats), and in rats with blockade of beta-adrenergic receptors (propranolol-treated rats). It was found in the fed control rats that both the heart glycogen and triglyceride levels were reduced at the beginning of the exercise and thereafter they returned to the control level despite the exercise being continued. The triglyceride level was reduced again during the exhaustive exercise. Reduced blood glucose supply increased the heart glycogen and triglyceride utilization during exercise. Partial prevention of the plasma FFA elevation during exercise increased the heart glycogen utilization and had no effect on utilization of the heart triglycerides. Blockade of the beta-adrenergic receptors fully prevented both the heart glycogen and triglyceride mobilization during exercise.This work was supported by the Polish Academy of Sciences, project No. 10.4.2.01.3.2.     

Exercise and energy intake: Effect of substrate oxidation

The main objective of this study was to evaluate the short-term effect of exercise-induced alteration in fat oxidation on postexercise spontaneous energy and macronutrient intakes. Eleven young males were submitted to two randomly assigned sessions of 48 h each, during which they were requested to eat in the laboratory. One of these sessions was preceded by a 90-min exercise bout at an intensity of 60% VO₂max. During both sessions, subjects ate ad lib food with a fat content conforming to the recommendations of nutrition agencies with a food quotient (FQ) ⩾ 0.85. Results showed that there was no significant change in postexercise energy and macronutrient intakes in comparison with the sedentary session. However, when subjects were subdivided into two groups on the basis of the respiratory quotient (RQ) measured during exercise, men with a low RQ (high fat oxidation) were characterized by a reduced postexercise increase in energy intake relative to the energy cost of exercise (ECE), i.e., they were more predisposed to be in negative posterexercise energy balance compared to those exhibiting a high RQ. Accordingly, exercise RQ was positively associated with postexercise energy and lipid balance. These results show that postexercise energy balance partly depends on the composition of the substrate mix oxidized during exercise.     

Mitochondrial uncoupling proteins: from mitochondria to the regulation of energy balance

The coupling of oxygen consumption to ADP phosphorylation is incomplete, as is particularly evident in brown adipocyte mitochondria which use a regulated uncoupling mechanism to dissipate heat produced by substrate oxidation. In brown adipose tissue, uncoupling is effected by a specific protein in the inner mitochondrial membrane referred to as uncoupling protein-1 (UCP1). UCP1 gene disruption in mice has confirmed UCP1's role in cold-induced thermogenesis. Genetic analysis of human cohorts has suggested that UCP1 plays a minor role in the control of fat content and body weight. The recent cloning of UCP2 and UCP3, two homologues of UCP1, has boosted research on the importance of respiration control in metabolic processes, metabolic diseases and energy balance. UCP2 is widely expressed in different organs whereas UCP3 is mainly present in skeletal muscle. The chromosomal localization of UCP2 as well as UCP2 mRNA induction by a lipid-rich diet in obesity-resistant mice suggested that UCP2 is involved in diet-induced thermogenesis. A strong linkage between markers in the vicinity of human UCP2 and UCP3 (which are adjacent genes) and resting metabolic rate was calculated. UCPs are known or supposed to participate in basal and regulatory thermogenesis, but their exact biochemical and physiological functions have yet to be elucidated. UCPs may constitute novel targets in the development of drugs designed to modulate substrate oxidation. However, very recent data suggest an important role for the UCPs in the control of production of free radicals by mitochondria, and in response to oxidants.     

Haematological and iron-related parameters in male and female athletes according to different metabolic energy demands

We investigated the iron-related haematological parameters in both male and female athletes participating in different sporting disciplines necessitating different metabolic energy demands. A total of 873 athletes (514 males, mean age: 22.08 ± 4.95 years and 359 females, mean age: 21.38 ± 3.88 years) were divided according to gender and to the predominant energy system required for participation in sport (aerobic, anaerobic or mixed) and haematological and iron-related parameters were measured. For both male and female athletes, significant differences related to the predominant energy system were found at a general level: male (Wilks’ λ = 0.798, F = 3.047, p < 0.001) and female (Wilks’ λ = 0.762, F = 2.591, p < 0.001). According to the ferritin cutoff value of 35 μg/L, whole body iron and sTfR significantly differed in all three groups of male and female athletes (p < 0.001). The percentage of hypochromic erythrocytes in male athletes was significantly higher only in those who required an anaerobic energy source (p < 0.001), whilst in the females hypochromic erythrocytes (p < 0.001) and haemoglobin (anaerobic, p = 0.042; mixed, p = 0.006) were significantly different only in anaerobic and mixed energy source athletes. According to the ferritin cutoff value of 22 μg/L, in females, whole body iron, sTfR and hypochromic erythrocytes were significantly higher in all three groups of athletes than those below the aforementioned cutoff value (p < 0.001). We conclude that the predominant energy system required for participation in sport affects haematological parameters. sTfR and body iron proved to be reliable parameters for monitoring the dynamics of iron metabolism and could contribute to successful iron-deficiency prevention.     

Molecular regulation of T lymphocyte homeostasis in the healthy and diseased immune system

Lymphocyte homeostasis is achieved by a balance between the production and death of lymphocytes. In particular, T lymphocytes differentiate and mature in the thymus and are released into the peripheral circulation, where they can travel to sites of encounter with antigen. Once in the circulation, T lymphocytes have varying life spans depending on whether they remain resting, become activated by antigen and replicate, or they become memory cells. The regulation of lymphocyte fate, especially the induction of programmed cell death, or apoptosis, has become a focus of intense molecular research, and much has been learned. In particular, the Fas receptor and other members of the tumor necrosis factor receptors, as well as their respective ligands, have emerged as key regulators of T lymphocyte apoptosis. We are studying genetic abnormalities of this death pathway, which we have found to underlie the human disease, autoimmune lymphoproliferative syndrome (ALPS). The study of ALPS has revealed that inhibiting the death of lymphocytes can lead to autoimmune consequences. Also, the homeostasis of T lymphocytes can be powerfully affected by viruses and other infectious agents. In particular, the human immunodeficiency virus can cause the attrition of CD4+ T lymphocytes by inducing the premature death of such cells. We are studying the molecular mechanism by which the HIV causes CD4+ T cell destruction.     

Brain volume regulation in response to changes in osmolality

Hypoosmolality and hyperosmolality are relatively common clinical problems. Many different factors contribute to the substantial morbidity and mortality known to occur during states of altered osmotic homeostasis. The brain is particularly vulnerable to disturbances of body fluid osmolality. The most serious complications are associated with pathological changes in brain volume: brain edema during hypoosmolar states and brain dehydration during hyperosmolar states. Studies in animals have elucidated many of the mechanisms involved with brain adaptation to osmotic stresses, and indicate that it is a complex process involving transient changes in water content and sustained changes in electrolyte and organic osmolyte contents. Appreciation of the nature of the adaptation process, and conversely the deadaptation processes that occur after recovery from hypoosmolality and hyperosmolality, enables a better understanding of the marked variations in neurological sequelae that characterize hyperosmolar and hypoosmolar states, and provides a basis for more rational therapies.     

Claudins: control of barrier function and regulation in response to oxidant stress

Claudins are a family of nearly two dozen transmembrane proteins that are a key part of the tight junction barrier that regulates solute movement across polarized epithelia. Claudin family members interact with each other, as well as with other transmembrane tight junction proteins (such as occludin) and cytosolic scaffolding proteins (such as zonula occludens-1 (ZO-1)). Although the interplay between all of these different classes of proteins is critical for tight junction formation and function, claudin family proteins are directly responsible for forming the equivalent of paracellular ion selective channels (or pores) with specific permeability and thus are essential for barrier function. In this review, we summarize current progress in identifying structural elements of claudins that regulate their transport, assembly, and function. The effects of oxidant stress on claudins are also examined, with particular emphasis on lung epithelial barrier function and oxidant stress induced by chronic alcohol abuse.