DNase γ, DNase I and caspase-activated DNase cooperate to degrade dead cells.

Serum endonucleases are essential for degrading the chromatin released from dead cells and preventing autoimmune diseases such as systemic lupus erythematosus. Serum DNase I is known as the major endonuclease, but recently, another endonuclease, DNase γ/DNase I-like 3, gained attention. However, the precise role of each endonuclease, especially that of DNase γ, remains unclear. In this study, we distinguished the activities of DNase γ from those of DNase I in mouse serum and concluded that both cooperated in degrading DNA during necrosis: DNase γ functions as the primary chromatolytic activity, causing internucleosomal DNA fragmentation, and DNase I as the secondary one, causing random DNA digestion for its complete degradation. These results were confirmed by two in vivo experimental mouse models, in which necrosis was induced, acetaminophen-induced hepatic injury and streptozotocin-induced ß-cell necrosis models. We also determined that DNase γ functions as a backup endonuclease for caspase-activated DNase (CAD) in the secondary necrosis phase after γ-ray-induced apoptosis in vivo.

Electrical properties of doped conjugated polyelectrolytes with modulated density of the ionic functionalities.

We report the synthesis of a series of water-soluble anionic narrow band-gap conjugated polyelectrolytes with a varied density of the ionic functional groups. The charge density is modulated by incorporating the structural units with tetraethylene glycol (TEG) monomethyl ether side chains. These polymers are readily p-doped during dialysis in water. CPEs with TEG side chains exhibit tighter intermolecular packing in the solid state and higher electrical conductivity.

Acrolein, a highly toxic aldehyde generated under oxidative stress in vivo, aggravates the mouse liver damage after acetaminophen overdose.

Although acetaminophen-induced liver injury in mice has been extensively studied as a model of human acute drug-induced hepatitis, the mechanism of liver injury remains unclear. Liver injury is believed to be initiated by metabolic conversion of acetaminophen to the highly reactive intermediate N-acetyl p-benzoquinoneimine, and is aggravated by subsequent oxidative stress via reactive oxygen species (ROS), including hydrogen peroxide (H2O2) and the hydroxyl radical (•OH). In this study, we found that a highly toxic unsaturated aldehyde acrolein, a byproduct of oxidative stress, has a major role in acetaminophen-induced liver injury. Acetaminophen administration in mice resulted in liver damage and increased acrolein-protein adduct formation. However, both of them were decreased by treatment with N-acetyl-L-cysteine (NAC) or sodium 2-mercaptoethanesulfonate (MESNA), two known acrolein scavengers. The specificity of NAC and MESNA was confirmed in cell culture, because acrolein toxicity, but not H2O2 or •OH toxicity, was inhibited by NAC and MESNA. These results suggest that acrolein may be more strongly correlated with acetaminophen-induced liver injury than ROS, and that acrolein produced by acetaminophen-induced oxidative stress can spread from dying cells at the primary injury site, causing damage to the adjacent cells and aggravating liver injury.

Nickeladihydrofuran. Key intermediate for nickel-catalyzed reaction of alkyne and aldehyde.

The formation of a nickeladihydrofuran by oxidative cyclization of an alkyne and an aldehyde with nickel(0) has been demonstrated; the transformation of the nickeladihydrofuran into an enone by decomposition, a lactone by carbonylation and an allylic alcohol by treatment with ZnMe(2) suggests that nickeladihydrofuran is an important key intermediate in a variety of catalytic reactions.

AlMe3-promoted oxidative cyclization of eta2-alkene and eta2-ketone on nickel(0). Observation of intermediate in methyl transfer process.

AlMe3 can promote the oxidative cyclization of eta2-alkene and eta2-ketone on nickel(0) to give an intriguing nickel-aluminum dinuclear complex having a bridging methyl group, which might be an intermediate for the nickel-catalyzed cycloisomerization of o-allylacetophenone or o-allylbenzophenone.