Increasing evidence suggests that the Bcl-2 family proteins play pivotal roles in regulation of the mitochondria cell-death pathway on transient cerebral ischemia. Bad, a BH3-only proapoptotic Bcl-2 family protein, has been shown to be phosphorylated extensively on serine by kinds of kinases. However, the exact mechanisms of the upstream kinases in regulation of Bad signaling pathway remain unknown. Here, we reported that Bad could be phosphorylated not only by Akt1 but also by JNK1/2 after transient global ischemia in rat hippocampal CA1 region. Our data demonstrated that Akt1 mediated the phosphorylation of Bad at serine 136, which increased the interaction of serine 136-phosphorylated Bad with 14-3-3 proteins and prevented the dimerization of Bad with Bcl-Xl, inhibited the release of cytochrome c to the cytosol and the death effector caspase-3 activation, leading to the survival of neuron. In contrast, JNK1/2 induced the phosphorylation of Bad at a novel site of serine 128 after brain ischemia/reperfusion, which inhibited the interaction of PI3K/Akt-induced serine 136-phosphorylated Bad with 14-3-3 proteins, thereby promoted the apoptotic effect of Bad. In addition, activated Akt1 inhibited the activation of Bad(S128) through downregulating JNK1/2 activation, thus inhibiting JNK-mediated Bad apoptosis pathway. Furthermore, the fate of cell to survive or to die was determined by a balance between prosurvival and proapoptotic signals. Taken together, our studies reveal that Bad phosphorylation at two distinct sites induced by Akt1 and JNK1/2 have opposing effects on ischemic brain injury, and present the possibility of Bad as a potential therapeutic target for stroke treatment.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.cellsig.2007.04.005 | DOI Listing |
J Adolesc Health
February 2025
San Francisco, California.
Aust Crit Care
January 2025
Centre for Quality and Patient Safety Research - Eastern Health Partnership, Box Hill, Victoria 3128, Australia; School of Nursing and Midwifery and Centre for Quality and Patient Safety in the Institute for Health Transformation, Deakin University, Geelong, Victoria 3125, Australia.
Background: The pandemic response required the large-scale redeployment of nurses to support the care of patients with COVID-19. Surveys of staff and analysis of staff feedback indicated that the frequent redeployment of intensive care unit (ICU) registered nurses (RNs) led to dissatisfaction and contributed to voluntary reductions in hours and increased intentions to resign. Whilst much is understood about the redeployment of non-ICU RNs into ICUs to support patient care during periods of high demand, less is known about ICU RNs' experiences of being redeployed to general wards.
View Article and Find Full Text PDFTransl Cancer Res
December 2024
Department of Hepatology and Gastroenterology, Campus Charité Mitte and Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and one of the leading causes of cancer-related deaths worldwide due to limited treatment options. The tumor microenvironment (TME), which is usually immunosuppressive in HCC, appears to be a decisive factor for response to immunotherapy and strategies aimed at inducing a more inflamed TME hold promise to overcome resistance to immunotherapy. Within the TME, the interplay of various cell types determines whether immunotherapy is successful.
View Article and Find Full Text PDFObstet Gynecol Surv
January 2025
Professor, Department of Biochemistry and Molecular Biology-A, University of Murcia, Murcia, Spain.
Importance: Infertility affects around 180 million people in the world and can be influenced by a number of nutritional factors.
Objective: The idea of a pretreatment optimization including beneficial weight loss, adequate physical activity, and good lifestyle habits could enhance fertility for many couples who want to conceive a baby.
Results: There are different aspects related to nutrition, such as obesity (affecting 23%-30% of reproductive-aged women), dietary patterns (type of diet, good or bad habits, and physical activity), nutrients (vitamins or minerals), hormones (adipokines, among others), and endocrine-disrupting chemicals (phytoestrogens and bisphenol A, among others) that have a clear impact on women's fertility.
Herzschrittmacherther Elektrophysiol
January 2025
, Bendorf, Deutschland.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!