BACKGROUND Doxorubicin treatment is known to cause muscular weakness. However, the cellular mechanisms have not been elucidated. We aimed to determine the effects of acute doxorubicin treatment on proteome lysine acetylation status, an indication of the apoptotic and inflammatory environment, and the expression and activation of various apical caspases involved in the initiation of apoptosis. ...

Expression profiling, ChiP-CHIP and phenotypic analysis were used to investigate the functional relationships of class III NAD(+)-dependent HDACs (Sirtuins) in fission yeast. We detected significant histone acetylation increases in Sirtuin mutants at their specific genomic binding targets and were thus able to identify an in vivo substrate preference for each Sirtuin. At heterochromatic loci, w...

Sirtuin 2 (SIRT2), a tubulin deacetylase, is a sirtuin family protein. SIRT2 inhibitors have been shown to decrease the cell death in cellular and Drosophila models of Parkinson's disease. However, SIRT2 decreases may also compromise cellular antioxidation capacity. Our current study found that silencing of SIRT2 led to a decrease in the intracellular ATP level of PC12 cells. We also found that...

Sirtuins have received considerable attention since the discovery that silent information regulator 2 (Sir2) extends the lifespan of yeast. Sir2, a nicotinamide adenine dinucleotide- (NAD-) dependent histone deacetylase, serves as both a transcriptional effector and energy sensor. Oxidative stress and apoptosis are implicated in the pathogenesis of neurodegenerative eye diseases. Sirtuins confe...

Blood vessels form the first organ in the developing embryo and build extensive networks that supply all cells with nutrients and oxygen throughout life. As blood vessels get older, they often become abnormal in structure and function, thereby contributing to numerous age-associated diseases including ischemic heart and brain disease, neurodegeneration, or cancer. First described as regulators ...

Nicotinamide adenine dinucleotide (NAD(+)) is an endogenous enzyme cofactor and cosubstrate that has effects on diverse cellular and physiologic processes, including reactive oxygen species generation, mitochondrial function, apoptosis, and axonal degeneration. A major goal is to identify the NAD(+)-regulated cellular pathways that may mediate these effects. Here we show that the dynamic assemb...

Huntington's disease (HD), an incurable neurodegenerative disorder, has a complex pathogenesis including protein aggregation and the dysregulation of neuronal transcription and metabolism. Here, we demonstrate that inhibition of sirtuin 2 (SIRT2) achieves neuroprotection in cellular and invertebrate models of HD. Genetic or pharmacologic inhibition of SIRT2 in a striatal neuron model of HD resu...