Sulforaphane, a constituent of many edible cruciferous vegetables, including broccoli, effectively suppresses proliferation of cancer cells in culture and in vivo by causing apoptosis induction, but the sequence of events leading to cell death is poorly defined. Here, we show that multidomain proapoptotic Bcl-2 family members Bax and Bak play a critical role in apoptosis induction by sulforapha...

Mitochondria are functionally and physically associated with heterotypic membranes, yet little is known about how these interactions impact mitochondrial outer-membrane permeabilization (MOMP) and apoptosis. We observed that dissociation of heterotypic membranes from mitochondria inhibited BAK/BAX-dependent cytochrome c (cyto c) release. Biochemical purification of neutral sphingomyelinases tha...

In Alzheimer's disease, cytochrome c-dependent apoptosis is a crucial pathway in neuronal cell death. Although beta-amyloid (Aβ) oligomers are known to be the neurotoxins responsible for neuronal cell death, the underlying mechanisms remain largely elusive. Here, we report that the oligomeric form of synthetic Aβ of 42 amino acids elicits death of HT-22 cells. But, when expression of a bcl-2 fa...

Platelets are anuclear cytoplasmic fragments essential for blood clotting and wound healing. Despite much speculation, the factors determining their life span in the circulation are unknown. We show here that an intrinsic program for apoptosis controls platelet survival and dictates their life span. Pro-survival Bcl-x(L) constrains the pro-apoptotic activity of Bak to maintain platelet survival...

Ultraviolet B (UVB) damage is recognized as the most important etiological factor in the development of skin cancer. Human papillomaviruses (HPV) have also been implicated in the disease, although the mechanism of action of these viruses remains unknown. We present evidence here that Bak protein is involved in signaling apoptosis in the skin in response to UVB damage, and that cutaneous HPV E6 ...

Purpose: Bax and Bak are regarded as key mediators for cytochrome c release and apoptosis. Loss of Bax or Bak is often reported in human cancers and renders resistance of these cancerous cells to chemotherapy. Here we investigated that phenylarsine oxide (PAO) could induce Bax/Bak-independent apoptosis. Experimental Design: Annexin V/PI staining, TUNEL staining and Caspase activation assays wer...

We analyze the behavior of the spatially anisotropic Bak-Sneppen model. We demonstrate that a nontrivial relation between critical exponents t and m5d/D , recently derived for the isotropic Bak-Sneppen model, holds for its anisotropic version as well. For the one-dimensional anisotropic Bak-Sneppen model, we derive an exact equation for the distribution of avalanche spatial sizes, and extract t...

Bcl-B protein is an anti-apoptotic member of the Bcl-2 family protein that contains all the four BH (Bcl-2 homology) domains (BH1, BH2, BH3 and BH4) and a predicted C-terminal transmembrane domain. Our previous results showed that Bcl-B binds Bax and suppresses apoptosis induced by over-expression of Bax; however, Bcl-B does not bind or suppress Bak. To explore the molecular basis for the diffe...

PURPOSE To investigate the safety of five types of antiglaucoma prostaglandin analog ophthalmic formulations, and to clarify their differences in accordance with contained additives (preservatives and surface-active agents). METHODS THE FOLLOWING FIVE TYPES OF OPHTHALMIC SOLUTIONS AND THREE TYPES OF ADDITIVES WERE INVESTIGATED: latanoprost (Xalatan(®); latanoprost), tafluprost (Tapros(®); taf...