Modulation of Apoptosis Pathways by Oxidative Stress and Autophagy in β Cells

Human islets isolated for transplantation are exposed to multiple stresses including oxidative stress and hypoxia resulting in significant loss of functional β cell mass. In this study we examined the modulation of apoptosis pathway genes in islets exposed to hydrogen peroxide, peroxynitrite, hypoxia, and cytokines. We observed parallel induction of pro- and antiapoptotic pathways and identified several novel genes including BFAR, CARD8, BNIP3, and CIDE-A. As BNIP3 is an inducer of autophagy, we examined this pathway in MIN6 cells, a mouse beta cell line and in human islets. Culture of MIN6 cells under low serum conditions increased the levels of several proteins in autophagy pathway, including ATG4, Beclin 1, LAMP-2, and UVRAG. Amino acid deprivation led to induction of autophagy in human islets. Preconditioning of islets with inducers of autophagy protected them from hypoxia-induced apoptosis. However, induction of autophagy during hypoxia exacerbated apoptotic cell death. ER stress led to induction of autophagy and apoptosis in β cells. Overexpression of MnSOD, an enzyme that scavenges free radicals, resulted in protection of MIN6 cells from cytokine-induced apoptosis. Ceramide, a mediator of cytokine-induced injury, reduced the active phosphorylated form of Akt and downregulated the promoter activity of the antiapoptotic gene bcl-2. Furthermore, cytokine-stimulated JNK pathway downregulated the bcl-2 promoter activity which was reversed by preincubation with SP600125, a JNK inhibitor. Our findings suggest that β cell apoptosis by multiple stresses in islets isolated for transplantation is the result of orchestrated gene expression in apoptosis pathway

Onset of Posttraumatic Stress Disorder and Major Depression Among Refugees and Voluntary Migrants to the United States

Although refugees are generally thought to be at increased risk for posttraumatic stress disorder (PTSD) and major depressive episode (MDE), few studies have compared onset of PTSD and MDE between refugees and voluntary migrants. Given differences in migration histories, onset should differ pre- and postmigration. TheNational Latino and Asian American Survey (NLAAS) is a national representative, complex dataset measuring psychiatric morbidity, mental health service use, and migration history among Latino and Asian immigrants to the United States. Of the 3,260 foreign-born participants, 660 were refugees (a weighted proportion of 9.52%). Refugees were more likely to report a history of war-related trauma, but reports of other traumatic events were similar. Premigration onset of PTSD was statistically higher for refugees than voluntary migrants, odds ratio (OR) = 4.86, 95% confidence interval (CI) [2.01, 11.76], where postmigration onset for PTSD was not, OR = 0.61, 95% CI [0.29, 1.28]; a similar pattern was found for MDE, OR = 1.98, 95% CI [1.11, 3.51]; and OR = 1.02, 95% CI [0.65, 1.62], respectively. Although refugees arrive in host countries with more pressing psychiatric needs, onset is comparable over time, suggesting that postmigration refugees and voluntary migrants may be best served by similar programs