Showing papers by "Lei Wei published in 2003"
TL;DR: Caspase 3 activation in heart failure sequentially cleaved SRF and generated a dominant-negative transcription factor, which may explain the depression of cardiac-specific genes, and caspase3 activation may be reversible in the failing heart with ventricular unloading.
Abstract: Background— Knowledge about molecular mechanisms leading to heart failure is still limited, but reduced gene activities and modest activation of caspase 3 are hallmarks of end-stage heart failure. We postulated that serum response factor (SRF), a central cardiac transcription factor, might be a cleavage target for modest activated caspase 3, and this cleavage of SRF may play a dominant inhibitory role in propelling hearts toward failure. Methods and Results— We examined SRF protein levels from cardiac samples taken at the time of transplantation in 13 patients with end-stage heart failure and 7 normal hearts. Full-length SRF was markedly reduced and processed into 55- and 32-kDa subfragments in all failing hearts. SRF was intact in normal samples. In contrast, the hearts of 10 patients with left ventricular assist devices showed minimal SRF fragmentation. Specific antibodies to N- and C-terminal SRF sequences and site-directed mutagenesis revealed 2 alternative caspase 3 cleavage sites, so that 2 fragment...
85 citations
TL;DR: DMPK enhanced SRF-mediated promoter activity of the skeletal and cardiac alpha-actin genes in C2C12 myoblasts as well as in nonmyogenic cells.
Abstract: Serum response factor (SRF) is a phosphoprotein that regulates skeletal and cardiac alpha-actin gene transcription. Myotonic dystrophy protein kinase (DMPK), a muscle- and neuron-restricted kinase, enhanced SRF-mediated promoter activity of the skeletal and cardiac alpha-actin genes in C2C12 myoblasts as well as in nonmyogenic cells. DMPK phosphorylated SRF in vitro in the alphaI coil of the DNA-binding domain in the MADS box, a highly conserved region required for DNA binding, dimerization, and co-activator interaction in COS and CV1 cells. Threonine 159 in the MADS box alphaI coil was a specific phosphorylation target in vitro as well as in vivo of both DMPK and protein kinase C-alpha. Substitution of threonine 159 with the nonphosphorylatable residue alanine markedly diminished activation of the cardiac alpha-actin promoter in the presence of kinase, while its substitution with aspartic acid, to introduce a negative charge and mimic phosphorylation, restored activation completely. Phosphorylation of the MADS box may constitute a novel mechanism for regulation of SRF-dependent actin gene transcription.
25 citations
TL;DR: In this paper, the formation mechanism of the stripes is discussed based on the Brusselator model and the self-assembled patterns on the Al surface strongly depend on the competition of the formation and the dissolution rate of alumina film during the reaction process.
9 citations
TL;DR: The striking variation in structural and labeling responses in the various zones and compartments indicate a heterogeneous tissue response in guinea pig OA that will probably affect sampling in biochemical analyses of cartilage homogenates and synovial fluid.
Abstract: We studied changes in the morphology of tibial articular cartilage in early guinea pig osteoarthrosis (OA) at 6 and 12 months of age with quantitative light microscopy, and the distribution of chon...
7 citations