Certain neurotrophins promote or induce oxidative neuronal death in cortical cultures. However, the effector mechanisms mediating this phenomenon have not been delineated. In this study, we investigated the possibility that NADPH oxidase and nitric oxide synthase (NOS) function as such effectors. Western blot analysis showed that treatment with brainderived neurotrophic factor (BDNF) and neurotrophin (NT)-4/5 increased the levels of NADPH oxidase subunits. Moreover, neurotrophin treatment resulted in membrane translocation of p67 phox , a characteristic feature of NADPH oxidase activation. Administration of the specific NADPH oxidase inhibitor, 4-(2-aminoethyl)benzenesulfonylfluoride (AEBSF), attenuated increases in oxygen free radicals thereby suggesting that NADPH oxidase contributes to the oxidative stress induced by neurotrophins. Furthermore, neuronal death induced by BDNF or NT-4/5 was significantly attenuated by AEBSF. Treatment with BDNF has previously been shown to induce neuronal NOS (nNOS). Our data indicated that inhibitors of nNOS attenuated neuronal death induced by BDNF or NT-4/5, consistent with an active role of nNOS in the mediation of neurotrophin neurotoxicity. As in other models of oxidative cell death, BDNF-induced neuronal death was accompanied by poly(ADP ribose) polymerase (PARP) activation. AEBSF or N-nitro-L-arginine (NNA) reduced BDNF-mediated PARP activation. PARP and poly(ADP ribose) glycohydrolase (PARG) are actively involved in mediating neurotrophin neurotoxicity since inhibitors of PARP and PARG significantly reduced levels of cell death. These results suggest that NADPH oxidase and nNOS contribute to increased oxidative stress, subsequent activation of PARP/PARG, and neuronal death induced by prolonged neurotrophin exposure.
The addition of various operator-dependent techniques to graded compression sonography is useful for allowing improved visualization of both normal and abnormal appendixes.
Breast cancer is one of the major female health problems worldwide. Although there is growing evidence indicating that air pollution increases the risk of breast cancer, there is still inconsistency among previous studies. Unlike the previous studies those had case-control or cohort study designs, we performed a nationwide, whole-population census study. In all 252 administrative districts in South Korea, the associations between ambient no 2 and particulate matter 10 (PM 10) concentration, and age-adjusted breast cancer mortality rate in females (from 2005 to 2016, N mortality = 23,565), and incidence rate (from 2004 to 2013, N incidence = 133,373) were investigated via multivariable beta regression. population density, altitude, rate of higher education, smoking rate, obesity rate, parity, unemployment rate, breastfeeding rate, oral contraceptive usage rate, and Gross Regional Domestic product per capita were considered as potential confounders. Ambient air pollutant concentrations were positively and significantly associated with the breast cancer incidence rate: per 100 ppb CO increase, odds Ratio oR = 1.08 (95% Confidence Interval CI = 1.06-1.10), per 10 ppb NO 2 , oR = 1.14 (95% CI = 1.12-1.16), per 1 ppb SO 2 , oR = 1.04 (95% CI = 1.02-1.05), per 10 µg/m 3 PM 10 , oR = 1.13 (95% ci = 1.09-1.17). However, no significant association between the air pollutants and the breast cancer mortality rate was observed except for PM 10 : per 10 µg/m 3 PM 10 , oR = 1.05 (95% CI = 1.01-1.09). Breast cancer is the most frequently diagnosed cancer among women worldwide 1 , and is rapidly increasing in industrialized countries and urban areas. In South Korea, breast cancer is the second most common after thyroid cancer and has annually increased by 6.1% from 1999 to 2014 2,3. Increased exposure to environmental female hormones is considered to affect the rise of breast cancer incidence. In addition, hormone-dependent cancer is increasing in industrialized countries 1,4. There is growing evidence indicating that air pollution is a risk factor for breast cancer. Nitrogen oxides (NO 2 and NO x) 5-9 , fine particulate matters (PM 10 and PM 2.5) 10,11 , and polycyclic aromatic hydrocarbons (PAHs) 12,13 are reported to associate with breast cancer incidence. The physiological mechanisms by which air pollutants affect breast cancer are largely explained in two ways. First, air pollutants may directly cause genetic mutations, as they are carcinogenic 14,15. Second, air pollutants may affect breast cancer incidence by increasing breast density, which is known to be a risk factor. Yaghjyan et al. reported an association between exposure to PM 2.5 , O 3 , and mammographic breast density 16. Female hormones affect breast density, and some air pollutants are known to exhibit endocrine-disrupting properties, including xenoestrogens 17. However, in the Danish Diet, Cancer and Health cohort (1993-1997) study, little evidence of association between traffic-related air pollution exposure and breast density was found 18. Hung et al. reported ...
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