Downregulation of the ERK 1 and 2 mitogen activated protein kinases using antisense oligonucleotides inhibits proliferation of porcine vascular smooth muscle cells

The current model of the arterial response to injury suggests that proliferation of vascular smooth muscle cells is a central event. Mitogen activated protein kinases are part of the final common pathway of intracellular signalling involved in cell division and thus constitute an attractive target in attempting to inhibit this proliferation. We hypothesised that antisense oligonucleotides to mitogen activated protein kinase would inhibit serum induced smooth muscle cell proliferation by downregulating the protein. Porcine vascular smooth muscle cells were cultured and an antisense oligonucleotide sequence against the ERK family of mitogen activated protein kinases (AMK1) was introduced by liposomal transfection. Sense oligonucleotides and a random sequence were used as controls. Proliferation was inhibited by AMK1 versus the sense controls, as assessed by tritiated thymidine incorporation (P<0.01). Immunoblots revealed downregulation of the target protein by AMK1 by 63% versus the sense control (P<0.05). In conclusion, antisense oligonucleotides specifically inhibited proliferation and downregulated the target protein. This is consistent with a central role for mitogen activated protein kinases in vascular smooth muscle cell proliferation in the porcine model. In addition, the data suggest a possible role for antisense oligonucleotides in the modulation of the arterial injury response

Differential response of root morphology to potassium deficient stress among rice genotypes varying in potassium efficiency*

Disparity in the root morphology of six rice (Oryza sativa L.) genotypes varying in potassium (K) efficiency was studied with three K levels: 5 mg/L (low), 10 mg/L (moderate) and 40 mg/L (adequate) in hydroponic culture. Morphological parameters included root length, surface area, volume and count of lateral roots, as well as fine (diameter<0.2 mm) and thick (diameter>0.2 mm) roots. The results indicate that the root growth of all genotypes was reduced under low K, but moderate K deficiency increased the root length of the efficient genotypes. At deficient and moderate K levels, all the efficient rice genotypes developed more fine roots (diameter<0.2 mm) than the inefficient ones. Both fine root count and root surface area were found to be the best parameters to portray K stress in rice. In accordance with the root morphology, higher K concentrations were noted in shoots of the efficient genotypes when grown at moderate and deficient K levels, indicating that root morphology parameters are involved in root uptake for K and in the translocation of K up to shoots. K deficiency affected not only the root morphology, but also the root ultra-structure. The roots of high-efficient genotypes had stronger tolerance to K deficient stress for root membrane damage, and could maintain the developed root architecture to adapt to the low K growth medium

Genome-Wide Association Study for Circulating Tissue Plasminogen Activator Levels and Functional Follow-Up Implicates Endothelial STXBP5 and STX2

Cardiolog