Effects of endocrine disrupting chemicals on expression of phospholipid hydroperoxide glutathione peroxidase mRNA in rat testes

Phospholipid hydroperoxide glutathione peroxidase (PHGPx), an antioxidative selenoprotein, is modulated by estrogen in the testis and oviduct. To examine whether potential endocrine disrupting chemicals (EDCs) affect the microenvironment of the testes, the expression patterns of PHGPx mRNA and histological changes were analyzed in 5-week-old Sprague-Dawley male rats exposed to several EDCs such as an androgenic compound [testosterone (50, 200, and 1,000 µg/kg)], anti-androgenic compounds [flutamide (1, 5, and 25 mg/kg), ketoconazole (0.2 and 1 mg/kg), and diethylhexyl phthalate (10, 50, and 250 mg/kg)], and estrogenic compounds [nonylphenol (10, 50, 100, and 250 mg/kg), octylphenol (10, 50, and 250 mg/kg), and diethylstilbestrol (10, 20, and 40 µg/kg)] daily for 3 weeks via oral administration. Mild proliferation of germ cells and hyperplasia of interstitial cells were observed in the testes of the flutamide-treated group and deletion of the germinal epithelium and sloughing of germ cells were observed in testes of the diethylstilbestrol-treated group. Treatment with testosterone was shown to slightly decrease PHGPx mRNA levels in testes by the reverse transcriptionpolymerase chain reaction. However, anti-androgenic compounds (flutamide, ketoconazole, and diethylhexyl phthalate) and estrogenic compounds (nonylphenol, octylphenol, and diethylstilbestrol) significantly upregulated PHGPx mRNA in the testes (p < 0.05). These findings indicate that the EDCs might have a detrimental effect on spermatogenesis via abnormal enhancement of PHGPx expression in testes and that PHGPx is useful as a biomarker for toxicity screening of estrogenic or antiandrogenic EDCs in testes

UVA ユウドウ ヒフ ヒカリロウカ ニオケル シシツ カサンカブツ ノ ヤクワリ ト コウサンカ ブッシツ セッシュ ノ エイキョウ

Role of ultraviolet A（UVA）on oxidative damage has attracted much attention in relation to skin photoaging process. In this study, we investigated effect of cholesterol hydroperoxides（Chol- OOHs）, stable products of reactive oxygen species（ROS）-induced lipid peroxidation, on matrix metalloproteinase（MMP）activation responsible for wrinkle formation in hairless mouse skin and then estimated the inhibition of UVA-induced MMP activation by dietary β-carotene. Hairless mice were exposed to UVA irradiation for 8 weeks. Chol-OOHs content in the skin was found to increase significantly by the exposure of UVA. In addition, the activity of MMP-9 and its protein expression were elevated with wrinkle formation. This activation was also induced by intracutaneous injection of Chol-OOHs. Interestingly, dietary β-carotene（500 mg/kg diet） and α-tocopherol （100 mg/kg diet）suppressed the accumulation of Chol-OOH as well as MMP activation. These results suggest that Chol-OOHs formed by the exposure of UVA to skin contribute to the activation of MMPs resulting in skin photoaging. Dietary antioxidants may prevent skin photoaging through, at least partly, the suppression of MMP activation due to UVA-induced lipid peroxidation

Improvement of Lipids and Reduction of Oxidative Stress With Octacosanol After Taekwondo Training

Athletes in combat sports undergo rapid changes in body weight prior to competition in order to gain a size advantage over their opponent. However, these large weight changes with concomitant high-intensity exercise training create poor lipid profiles and high levels of oxidative stress, which can be detrimental to health and sport performance. Therefore, the purpose of this study was to investigate the ability of the nutritional supplement octacosanol to combat the physiological detriments that occur in taekwondo players during rapid weight loss with high-intensity exercise training. Methods: A total of 26 male taekwondo players were randomly divided into 2 groups: An experimental group performed a 5% weight-loss and taekwondo training program with 40-mg octacosanol intake (OCT; n = 13) for 6 d, and a control group performed the same weight-loss and taekwondo training program with a placebo (CON; n = 13). Results: There were significant (P \u3c .05) group × time interactions for low-density lipoprotein and triglycerides, which significantly decreased (Δ18 [5] mg/dL and Δ80 [7] mg/dL, respectively), and high-density lipoprotein, which significantly increased (Δ10 [7] mg/dL), in the OCT group compared with the CON group. There were also significant (P \u3c .05) group × time interactions for superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA), with SOD increasing (Δ226 [121] U/gHb) in the OCT group, while GPx decreased (Δ20 [13] U/gHb) and MDA increased (Δ72 [0.04] nmol/mL) in the CON group. Conclusion: These results suggest that octacosanol may be a beneficial supplement to protect against the poor cholesterol levels and oxidative stress that occurs during taekwondo training

Oxidant-NO dependent gene regulation in dogs with type I diabetes: impact on cardiac function and metabolism

<p>Abstract</p> <p>Background</p> <p>The mechanisms responsible for the cardiovascular mortality in type I diabetes (DM) have not been defined completely. We have shown in conscious dogs with DM that: <it>1</it>) baseline coronary blood flow (CBF) was significantly decreased, <it>2</it>) endothelium-dependent (ACh) coronary vasodilation was impaired, and <it>3</it>) reflex cholinergic NO-dependent coronary vasodilation was selectively depressed. The most likely mechanism responsible for the depressed reflex cholinergic NO-dependent coronary vasodilation was the decreased bioactivity of NO from the vascular endothelium. The goal of this study was to investigate changes in cardiac gene expression in a canine model of alloxan-induced type 1 diabetes.</p> <p>Methods</p> <p>Mongrel dogs were chronically instrumented and the dogs were divided into two groups: one normal and the other diabetic. In the diabetic group, the dogs were injected with alloxan monohydrate (40-60 mg/kg iv) over 1 min. The global changes in cardiac gene expression in dogs with alloxan-induced diabetes were studied using Affymetrix Canine Array. Cardiac RNA was extracted from the control and DM (n = 4).</p> <p>Results</p> <p>The array data revealed that 797 genes were differentially expressed (P < 0.01; fold change of at least ±2). 150 genes were expressed at significantly greater levels in diabetic dogs and 647 were significantly reduced. There was no change in eNOS mRNA. There was up regulation of some components of the NADPH oxidase subunits (gp91 by 2.2 fold, P < 0.03), and down-regulation of SOD1 (3 fold, P < 0.001) and decrease (4 - 40 fold) in a large number of genes encoding mitochondrial enzymes. In addition, there was down-regulation of Ca²⁺cycling genes (ryanodine receptor; SERCA2 Calcium ATPase), structural proteins (actin alpha). Of particular interests are genes involved in glutathione metabolism (glutathione peroxidase 1, glutathione reductase and glutathione S-transferase), which were markedly down regulated.</p> <p>Conclusion</p> <p>our findings suggest that type I diabetes might have a direct effect on the heart by impairing NO bioavailability through oxidative stress and perhaps lipid peroxidases.</p

Детерминанты ферроптоза - потенциальные терапевтические мишени стволовых клеток глиобластомы

Introduction. Treatment of glioblastoma multiforme remains little effective due to the rapidly developing recurrence of the tumor, due to its high tumorigenic potential, resistance to chemoradiation therapy and increased dissemination of glioma stem cells. The identification of potential therapeutic targets, which make it possible to more effectively destroy glioma stem cells, becomes topical. In this regard, the study of ferroptosis (FP), which can cause the death of tumor cells with a highly malignant phenotype, is of great importance. However, FP and its regulatory pathways in the GSC are not fully understood. At present, it is also not clear how FP differs for glioma stem cells and glioblastoma differentiated cells.Aim. To study the expression of ferroptosis signaling cascade determinants in CD133+ glioma stem cells and CD133- glioblastoma differentiated cells using high resolution proteomic mass spectrometry.Materials and methods. High-resolution proteomic mass spectrometry, cell technologies.Results. In total, 1970 proteins were identified, 15 of which are associated with ferroptosis and are present in both cell populations. Upregulation of 12 FP determinants (ACSL1, ACSL3, COPZ1, FTH1, FTL, GPX1, GPX4, PCBP1, SLC3A2, TFRC, VDAC1, VDAC2) was found in CD133+ glioblastoma stem cells compared to CD133- differential glioblastoma cells, 10 of which were more than 2-fold overexpressed.Conclusion. Important regularities have been established in the expression of ferroptosis determinants and proteins controlling this process in glioma stem cells, which can be used in the development of new approaches to the detection of potential targets for the therapy of glioblastoma multiforme.Введение. Терапия мультиформной глиобластомы остается малоэффективной из-за быстроразвивающихся рецидивов опухоли, обусловленных высоким туморогенным потенциалом, резистентностью к химиолучевой терапии и повышенной диссеминацией стволовых клеток глиобластомы. Актуальной становится идентификация потенциальных терапевтических мишеней, позволяющих более эффективно уничтожать данные клетки. в связи с этим большое значение приобретает изучение ферроптоза (ФП), способного вызывать гибель опухолевых клеток с высокозлокачественным фенотипом. Однако ФП и его регуляторные пути в стволовых клетках глиобластомы до конца не изучены. в настоящее время также не ясно, чем отличается ФП в стволовых и дифференцированных клетках глиобластомы.Цель исследования - методом протеомной масс-спектрометрии высокого разрешения изучить экспрессию детерминант сигнального каскада ФП в CD133+-стволовых и CD133--дифференцированных клетках глиобластомы.Материалы и методы. использовались протеомная масс-спектрометрия высокого разрешения и клеточные технологии.Результаты. в целом идентифицированы 1970 белков, 15 из которых связаны с ФП и присутствуют в обеих популяциях клеток. Обнаружена положительная регуляция 12 детерминант ФП (ACSL1, ACSL3, COPZ1, FTH1, FTL, GPX1, GPX4, PCBP1, SLC3A2, TFRC, VDAC1, VDAC2) в CD133+-стволовых клетках глиобластомы по сравнению с CD133- -дифференцированными клетками глиобластомы, 10 из которых имели повышенную более чем в 2 раза экспрессию.Заключение. Установлены важные закономерности в экспрессии детерминант ФП и протеинов, контролирующих этот процесс в стволовых клетках глиобластомы, которые могут использоваться при разработке новых подходов к обнаружению потенциальных мишеней для терапии мультиформной глиобластомы

Selenium-induced senescence involves heterochromatin formation

Abstract We have recently shown that selenium compounds can induce a senescence response in a manner depending on ataxia-telangiectasia mutated (ATM), DNA-dependent protein kinase (DNA-PK), p53 and reactive oxygen species (ROS). To test the hypothesis that the selenium-induced senescence response involves epigenetic changes in senescence-associated heterochromatin foci (SAHF), we determined the expression of histone H3 Lysine 9 trimethylation (H3K9me3), a marker of SAHF, in human primary MRC-5 cells treated with methylseleninic acid (MSeA, 2 &#956;M) for 2 days, followed by a 7-day recovery, in the presence or absence of KU55933 (10 &#956;M), an ATM kinase inhibitor, and NU7026 (10 &#956;M), a DNA-PK kinase inhibitor. Our results showed that MSeA treatment induced the formation of SAHF and H3K9me3 foci. Pre-treatment of the cells with KU55955 or NU7026 resulted in numerous and smaller foci, and they did not co-localize with the MSeA-induced SAHF. These results suggest that the MSeA-induced senescence response involves epigenetic changes of H3K9me3 in a manner depending on ATM and DNA-PK