Most intrinsic death signals converge into the activation of pro-apoptotic BCL-2 family members BAX and BAK at the mitochondria, resulting in the release of cytochrome c and apoptosome activation. Chronic endoplasmic reticulum (ER) stress leads to apoptosis through the upregulation of a subset of pro-apoptotic BH3-only proteins, activating BAX and BAK at the mitochondria. Here we provide eviden...

The increased longevity of the C. elegans electron transport chain mutants isp-1 and nuo-6 is mediated by mitochondrial ROS (mtROS) signaling. Here we show that the mtROS signal is relayed by the conserved, mitochondria-associated, intrinsic apoptosis signaling pathway (CED-9/Bcl2, CED-4/Apaf1, and CED-3/Casp9) triggered by CED-13, an alternative BH3-only protein. Activation of the pathway by a...

The sesquiterpene lactone dihydroartemisinin (DHA), a semisynthetic derivative of the herbal antimalaria drug artemisinin, is cytotoxic to human tumor cells. Treatment of Jurkat T-lymphoma cells with DHA induced a breakdown of the mitochondrial transmembrane potential, release of cytochrome c, activation of caspases, and DNA fragmentation indicative of apoptosis induction. Although the absence ...

The canonical Wnt-pathway plays a number of crucial roles in the development of organism. Malfunctions of this pathway lead to various diseases including cancer. In the inactivated state, this pathway involves five proteins, Axin, CKI-α, GSK-3β, APC, and β-catenin. We analyzed these proteins by a number of computational tools, such as PONDR(r)VLXT, PONDR(r)VSL2, MoRF-II predictor and Hydrophobi...

Procedural memories and habits are posited to be stored in the basal ganglia, whose intrinsic circuitries possess important inhibitory connections arising from striatal spiny neurons. However, no information about long-term plasticity at these synapses is available. Therefore, this work describes a novel postsynaptically dependent long-term potentiation (LTP) at synapses among spiny neurons (in...

Apoptosis, the cell's natural mechanism for death, is a promising target for anticancer therapy. Both the intrinsic and extrinsic pathways use caspases to carry out apoptosis through the cleavage of hundreds of proteins. In cancer, the apoptotic pathway is typically inhibited through a wide variety of means including overexpression of antiapoptotic proteins and under-expression of proapoptotic ...

Parallel ON and OFF pathways conduct visual signals from bipolar cells in the retina to higher centers in the brain. ON responses are thought to originate by exclusive use of metabotropic glutamate receptor 6 (mGluR6) expressed in retinal ON bipolar cells. Paradoxically, we find ON responses in retinal ganglion cells of mGluR6-null mice, but they occur at long latency. The long-latency ON respo...

autoimmune lymphoproliferative syndrome (alps) is a prototypic disorder of abnormal lymphocyte homeostasis. in the september 2005 issue of the iranian journal of allergy, asthma and immunology, a patient with clinical features consistent with alps was described. although the clinical presentation was in favor of alps, a precise diagnosis needed more laboratory evaluations.

The striatum is widely viewed as the fulcrum of pathophysiology in Parkinson's disease (PD) and L-DOPA-induced dyskinesia (LID). In these disease states, the balance in activity of striatal direct pathway spiny projection neurons (dSPNs) and indirect pathway spiny projection neurons (iSPNs) is disrupted, leading to aberrant action selection. However, it is unclear whether countervailing mechani...

BACKGROUND Endogenous sphingolipid signaling has been shown to play an important role in prostate cancer endocrine resistance. METHODS The novel SphK2 inhibitor, ABC294640, was used to explore SphK signaling in androgen resistant prostate cancer cell death signaling. RESULTS It dose-dependently decreased PC-3 and LNCaP cell viability, IC(50) of 28 ± 6.1 μM (p < 0.05) and 25 ± 4.0 μM (p < 0....