Redox homeostasis of albumin in relation to alpha-lipoic acid and dihydrolipoic acid

Albumin represents the predominant circulating antioxidant agent in plasma exposed to continuous oxidative stress and a change in serum albumin structure accounts for its antioxidant properties. Alterations in the redox status of albumin may result in impairments of its biological properties. Alpha-lipoic acid (LA), a naturally occurring thiol compound found in virtually all species, is a potent antioxidant with high efficacy which is also involved in the chelation of metal ions, regeneration of antioxidants, and repair of oxidatively damaged proteins. In human body LA is rapidly reduced to dihydrolipoic acid (DHLA) after intake into the cell. Both, LA and DHLA are amphipathic molecules which act as antioxidants both in hydrophilic and lipophilic environments. The present study aimed to investigate the antioxidant/pro-oxidant effects of LA and DHLA due to their concentrations in metal-catalyzed protein oxidation (MCO) of human serum albumin (HSA). Progressive oxidative modification of albumin was found in MCO system by an increased content of protein hydroperoxides (POOH), protein carbonyl groups (PCO) which is the former's major breakdown product, and other protein oxidation markers such as advanced oxidized protein products (AOPP) and protein thiol groups (P-SH). The possible antioxidant protective effects of LA and DHLA were observed with 25 µM and 50 µM; DHLA being more influential. Protein oxidation parameters were found to be lower and P-SH levels seemed higher. However, prooxidant effects of both LA and DHLA came on the scene with increased concentrations of 75 µM and 100 µM where the latter seemed the most hazardous with contradicted results. It is clear that the loss of biological activity of human serum albumin by MCO system appears of medical relevance and if LA exerts similar effects seen in the present study, it is possible that cellular prooxidant activity can also result consuming this unique antioxidant in certain doses

Exercise training with dietary counselling increases mitochondrial chaperone expression in middle-aged subjects with impaired glucose tolerance

<p>Abstract</p> <p>Background</p> <p>Insulin resistance and diabetes are associated with increased oxidative stress and impairment of cellular defence systems. Our purpose was to investigate the interaction between glucose metabolism, antioxidative capacity and heat shock protein (HSP) defence in different skeletal muscle phenotypes among middle-aged obese subjects during a long-term exercise and dietary intervention. As a sub-study of the Finnish Diabetes Prevention Study (DPS), 22 persons with impaired glucose tolerance (IGT) taking part in the intervention volunteered to give samples from the <it>vastus lateralis </it>muscle. Subjects were divided into two sub-groups (IGTslow and IGTfast) on the basis of their baseline myosin heavy chain profile. Glucose metabolism, oxidative stress and HSP expressions were measured before and after the 2-year intervention.</p> <p>Results</p> <p>Exercise training, combined with dietary counselling, increased the expression of mitochondrial chaperones HSP60 and glucose-regulated protein 75 (GRP75) in the <it>vastus lateralis </it>muscle in the IGTslow group and that of HSP60 in the IGTfast group. In cytoplasmic chaperones HSP72 or HSP90 no changes took place. In the IGTslow group, a significant positive correlation between the increased muscle content of HSP60 and the oxygen radical absorbing capacity values and, in the IGTfast group, between the improved VO_2maxvalue and the increased protein expression of GRP75 were found. Serum uric acid concentrations decreased in both sub-groups and serum protein carbonyl concentrations decreased in the IGTfast group.</p> <p>Conclusion</p> <p>The 2-year intervention up-regulated mitochondrial HSP expressions in middle-aged subjects with impaired glucose tolerance. These improvements, however, were not correlated directly with enhanced glucose tolerance.</p

Streptozotocin, Type I Diabetes Severity and Bone

As many as 50% of adults with type I (T1) diabetes exhibit bone loss and are at increased risk for fractures. Therapeutic development to prevent bone loss and/or restore lost bone in T1 diabetic patients requires knowledge of the molecular mechanisms accounting for the bone pathology. Because cell culture models alone cannot fully address the systemic/metabolic complexity of T1 diabetes, animal models are critical. A variety of models exist including spontaneous and pharmacologically induced T1 diabetic rodents. In this paper, we discuss the streptozotocin (STZ)-induced T1 diabetic mouse model and examine dose-dependent effects on disease severity and bone. Five daily injections of either 40 or 60 mg/kg STZ induce bone pathologies similar to spontaneously diabetic mouse and rat models and to human T1 diabetic bone pathology. Specifically, bone volume, mineral apposition rate, and osteocalcin serum and tibia messenger RNA levels are decreased. In contrast, bone marrow adiposity and aP2 expression are increased with either dose. However, high-dose STZ caused a more rapid elevation of blood glucose levels and a greater magnitude of change in body mass, fat pad mass, and bone gene expression (osteocalcin, aP2). An increase in cathepsin K and in the ratio of RANKL/OPG was noted in high-dose STZ mice, suggesting the possibility that severe diabetes could increase osteoclast activity, something not seen with lower doses. This may contribute to some of the disparity between existing studies regarding the role of osteoclasts in diabetic bone pathology. Examination of kidney and liver toxicity indicate that the high STZ dose causes some liver inflammation. In summary, the multiple low-dose STZ mouse model exhibits a similar bone phenotype to spontaneous models, has low toxicity, and serves as a useful tool for examining mechanisms of T1 diabetic bone loss

EVALUATION OF PAID MILITARY SERVICE IN TURKEY USING A POPULATION REPRESENTATION MODEL

This research examines paid military service in Turkey utilizing the Population Representation Model introduced originally by M. J. Eitelberg in 1979. Despite the worldwide trend toward professional militaries, Turkey is one of few countries that relies on a universal draft for its military manpower. Every year, thousands of young men are enlisted for six to twelve months; however, eligible men have the option to purchase a paid exemption from compulsory military service. The most recent paid military service exemption law was introduced in August 2018 and requires a fee of $2,700. Because many diverse governments in Turkey have introduced military buy-out laws, it can be argued that this exemption practice is seen as legitimate in the country. On the other hand, in terms of social equity, the exemption laws may be changing the composition of the Turkish military by underrepresenting certain segments of Turkish society within the force. While paid exemption laws can help to increase the proportion of professional members and ultimately strengthen the effectiveness of the Turkish military, recent exemption laws have created a historically large gap in the draftee corps. Therefore, it might be better if Turkey stops offering the option of paid exemption based on temporary laws. If there is an excess of young men in the population, the exemption laws could be revised and applied permanently to uphold the principle of “equality before the law.”http://archive.org/details/evaluationofpaid1094562235First Lieutenant, Turkish Air ForceApproved for public release; distribution is unlimited

Pro-oxidant actions of alpha-lipoic acid and dihydrolipoic acid

There is strong accumulating evidence that a a-lipoic acid (LA) supplement is good insurance, and would markedly improve human health. LA is readily absorbed from the diet, transported to cells and reduced to dihydrolipoic acid (DHLA). Of the two compounds, DHLA evidently has greater antioxidant activity. Much research has focused on the antioxidant properties of these compounds. Aside from its antioxidant role, in vitro and in vivo studies suggest that LA and its reduced form DHLA also act as a pro-oxidant properties. Limited number of studies concerning the pro-oxidant potential of LA and DHLA were performed only in recent years. The ability of LA and/or DHLA to function as either anti- or pro-oxidants, at least in part, is determined by the type of oxidant stress and the physiological circumstances. These pro-oxidant actions suggest that LA and DHLA act by multiple mechanisms, many of which are only now being explored. LA has been reported to have a number of potentially beneficial effects in both prevention and treatment of oxygen-related diseases. Selection of appropriate pharmacological doses of LA for use in oxygen-related diseases is critical. On the other hand, much of the discussion in clinical studies has been devoted to the pro-oxidant role of LA. This aspect remains to be elucidated. In further studies, careful evaluation will be necessary for the decision in the biological system whether LA administration is beneficial or harmful. (c) 2005 Elsevier Ltd. All rights reserved

Protein Redox-Regulation Mechanisms in Aging

The perspicuity of the general mechanisms of in vivo protein oxidation was achieved in the 1980s and that of the redox-homeostasis mechanisms of reactive oxygen species (ROS)/antioxidants in the 1990s. Publications in the scientific literature dealing with protein redox-regulation mechanisms in aging have appeared only within the past 10-15 years. As is well known, the group of protein disulfide oxidoreductases, such as thioredoxin (Trx), glutaredoxin, and Trx-dependent oxidoreductases, as well as methionine sulfoxide reductase (Msr), and the mechanisms related to these systems work synergistically to regulate the level of oxidized proteins and to repair mildly oxidatively modified proteins, keeping a balanced redox potential to maintain the function of aging cells. The proteolytic enzyme systems such as proteasome complexes, caspases, and the Lon protease, which are regulated by redox mechanisms, eliminate oxidized proteins. These mechanisms, in turn, affect redox homeostasis of proteins in aging cells. The ubiquitination and sumoylation of proteins are other mechanisms by which selectively oxidized proteins are targeted for degradation and compartmentalization with such specificity believed to be necessary for maintenance of cellular redox homeostasis. However, some of the extensively oxidized proteins of an unrepairable nature can escape degradation pathways and form high-molecular-weight aggregates that accumulate with age. Such oxidized protein aggregates can become cytotoxic and have been associated with a large number of age-related disorders, including Alzheimer's disease, Parkinson's disease, cataractogenesis, and cancer. Considering the variations that have emerged in redox-regulation mechanisms and antioxidant systems related to age-related disorders, it is found that these are of an extremely complex nature. Work communicated to us in the current scientific literature now shows the extent of oxidative protein damage in aged subjects and in age-related disorders. Future research will probably be concerned with understanding the relationship between the aforementioned redox-regulatory proteins and age-related disorders. Such scientific progress will bring preventive and therapeutic approaches to control altered redox homeostasis in these disorders