Smoking induces oxidative stress inside the Graafian follicle

BACKGROUND: A growing body of evidence indicates that pro-oxidant/antioxidant balance inside ovarian follicles plays an important role in folliculogenesis. Over 20% of women of reproductive age in Europe and the USA regularly smoke cigarettes. The impact of tobacco smoking on the intrafollicular markers of oxidative stress has not been fully elucidated. The objective of the present study was to test the hypothesis that cigarette smoking affects the intrafollicular redox milieu. METHODS: In follicular fluid samples originating from 108 IVF patients, lipid peroxidation was assessed by the thiobarbituric reactive substances method and total antioxidative capacity was quantified by the luminol enhanced chemiluminescence method. The level of patients' exposure to the cigarette smoke was evaluated by measuring the follicular fluid cotinine concentration by means of radioimmunoassay. RESULTS: Intrafollicular exposure to cigarette smoke metabolites was associated with a significant increase in follicular lipid peroxidation intensity (P < 0.001), which was accompanied by a significant decrease in the local antioxidative potential (P = 0.004). CONCLUSION: The results indicate that active smoking affects the pro-oxidant/antioxidant balance inside the pre-ovulatory ovarian follicle by inducing intrafollicular oxidative stress. This provides another possible explanation for impaired folliculogenesis in female smokers.     

pH modulates conducting and gating behaviour of single calcium release channels

Intracellular pH changes affect excitation-contraction coupling in skeletal, and cardiac muscles. However the proton implication in modulating the sarcoplasmic reticulum Ca²⁺ release channel activity has never been visualized at single channel level. A large conducting Ca²⁺ release pathway has previously been characterized after incorporation of skeletal and cardiac sarcoplasmic reticulum vesicles into planar lipid bilayers. This channel has been activated by micromolar and millimolar concentrations of Ca²⁺ and ATP, respectively. The pH was independently varied on each side of the channels. Acidification of the cis-chamber (7.4 to 6.6) induced a modification of the gating behaviour, resulting in a decrease of the open probability. This effect was completely reversible. On the other hand, acidification of the trans-chamber (7.4 to 6.8) induced a reduction of the unitary conductance of the sarcoplasmic reticulum Ca²⁺ release channel.     

PLPP2: Potential therapeutic target of breast cancer in PLPP family

PLPPs (Phospholipid phosphatases) are widely expressed in different human tissues, regulate cell signal transduction, and are overexpressed in cancers such as gliomas, pancreatic adenocarcinoma, lung adenocarcinoma, and so on. As a member of the PLPP family, PLPP2 (phospholipid phosphatase 2) plays a vital role in the occurrence and development of breast cancer, but its mechanism is still unclear. Our research found that PLPP2 was overexpressed in breast cancer, and the higher expression level of PLPP2 showed a worse prognosis for breast cancer patients. Further analysis showed that overexpression of PLPP2 affected the expression of CDC34 (cell-division cycle 34), LSM7 (Like-Smith 7), and SGTA (small glutamine-rich tetratricopeptide repeat-containing protein alpha) through EMT (epigenetic-mesenchymal transition) related pathways to promote the occurrence and development of breast cancer. In vitro, silencing PLPP2 significantly reduced the proliferation, invasion, and migration abilities of human breast cancer cells MDA-MB-231. ER+ is a common subtype of breast cancer. Furthermore, we found that the overexpression of PLPP2 was significantly related to the poor prognosis of ER+ breast cancer. These results indicate that PLPP2 has value as a potential therapeutic target for breast cancer, especially for ER+ breast cancer.     

Changes in activity of superoxide dismutase in the human endometrium throughout the menstrual cycle and in early pregnancy

To investigate the possible role of the superoxide radical andits scavenging system in the human endometrium, the immunohistochemicaldistribution of superoxide dismutase (SOD), activities of SODand lipid peroxide concentrations were studied in the humanendometrium throughout the menstrual cycle and in early pregnancy.The endometrial epithelium showed a positive immunostainingfor Cu, Zn-SOD and Mn-SOD throughout the entire menstrual cycleand in early pregnancy. In the stroma, weak immunostaining forCu, Zn-SOD and moderate immunostaining for Mn-SOD were observedin the predecidual cells in the late secretory phase. Decidualcells in early pregnancy showed strong immunostaining for Cu,Zn-SOD and Mn-SOD. Total SOD activity in theendometrium increasedfrom early proliferative phase to mid-late proliferative phaseand further increased in the mid-secretory phase, and decreasedin the late secretory phase. The total SOD activity in the endometriumofearly pregnancy was the same level as that in the mid-secretoryphase. Cu, Zn-SOD and Mn-SOD activitieschanged in a similarmanner to total SOD activity throughout the menstrual cycleand in early pregnancy. Lipid peroxide concentration in theendometrium increased from early proliferative phase to mid-lateproliferativephase and further increased in the late secretoryphase. However, lipid peroxide concentration in theendometriumof early pregnancy was the same as that in the midsecretoryphase. These results suggested thatthe superoxide radical andits scavenging system may play an important role in the regulationof humanendometrial function.     

apoH基因多态性与脑卒中的相关性研究及其对血脂的影响

目的：探讨载脂蛋白H（apolipoprotein H,apoH）基因第8外显子G1025C（Try316Ser）多态性与长沙地区汉族人脑卒中的关系及其对血 脂的影响。方法：采用PCR－单链构象多态技术和DNA直接测序法检测长沙地区汉族260例脑卒中患者、20个脑卒中家系成员和100名健康对照者的apoH基因第8外显子G1025C（Try316Ser）多态性；酶联免疫吸附法检测抗磷脂抗体水平；酶法测定总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL－C）、低密度脂蛋白胆固醇（LDL－C），免疫比浊法测定apoA-I及apo B100，酶联免疫吸附法测定脂蛋白a血清水平。结果：长沙地区汉族人apoH基因G1025C（Try316Ser）多态存在GG、GC两种基因型，脑卒中组及其各亚组G1025C（Try316Ser）多态基因频率分布与对照组比较差异无显著性（P＞0．05）；分析不同基因型对血脂、脂蛋白水平的影响，发现脑梗塞组和对照组GC基因型血清TG水平均明显高于GG基因型（P＜0．05）。结论：长沙地区汉族人apoH基因G1025C（Try316Ser）多态性可能与脑卒中的易患性无关，但与血脂代谢有一定关联。     

Effects of fibrinogen on lipid peroxidation in patients with coronary heart disease and in vitro

In patients with coronary heart disease oxidizability of lipids during Cu²⁺-induced oxidation of blood plasma inversely correlated with fibrinogen content. A positive correlation was found between the amount of lipid peroxidation products in the plasma from these patients and fibrinogen content. The increase in fibrinogen content was associated with high levels of total lipids and triglycerides and low concentration of high-density lipoprotein cholesterol. In vitro experiments demonstrated that fibrinogen reduces oxidizability of blood plasma. Our results suggest that the decrease in lipid oxidizability at high concentration of fibrinogen in patients with coronary heart disease is related to predominant oxidation of fibrinogen and its competition with plasma lipids during Cu²⁺-induced oxidation.     

Relationship between oxidative stress and embryotoxicity of hydrosalpingeal fluid

BACKGROUND: Oxidative stress mechanisms are involved in the pathophysiology of many reproductive disorders. The objective of this study was to characterize oxidative stress parameters in hydrosalpingeal fluid (HSF) and examine their possible role in early embryo development. METHODS AND RESULTS: HSF was aspirated at laparoscopic salpingectomy in 11 infertile women. Reactive oxygen species (ROS), total (non-enzymatic) antioxidant capacity (TAC) and lipid peroxidation (LPO) were assayed. Two-cell mouse embryos were incubated with 25, 50 or 75% HSF and the blastocyst development rate was observed. ROS was detected in five of 11 (45%) HSF samples with a mean of 4.2 x 10(4) c.p.m. LPO was detected in all samples at a mean (+/- SD) value of 5575.4 +/- 6091.9 micromol/l malonaldehyde. The mean blastocyst development rate at 25, 5+/- 0 and 75% HSF and in the control group was 88.9 +/- 9.4, 65.7 +/- 19.1, 45.7 +/- 5.7 and 96.7% respectively (P < 0.0001). The blastocyst development rate was positively correlated to ROS concentrations (P < 0.02) but was not significantly related to LPO. CONCLUSIONS: The blastocyst development rate decreased with increasing concentrations of HSF. For the first time, the presence of ROS, LPO and TAC activity in human HSF was characterized. A possible role of oxidative stress in the embryotoxicity of HSF is suggested.     

Primary biliary cirrhosis and coronary atherosclerosis: Protective antioxidant effect of bilirubin

Increased concentration of lipid peroxidation products in patients with primary biliary cirrhosis is related to elevation of serum lipid content, but not to activation of lipid peroxidation. Hyperbilirubinemia in patients with primary biliary cirrhosis is accompanied by a decrease in the concentration of lipid peroxidation products and increase in antioxidant activity of blood serum. Antioxidants play a major role in the prevention of atherosclerosis. We hypothesized that the absence of increased risk of atherosclerosis in patients with primary biliary cirrhosis is due to inhibition of lipid peroxidation in blood serum by antioxidant compound bilirubin. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 1, pp. 23–28, January, 2008