Allelic Variation in the Toll-Like Receptor Adaptor Protein Contributes to SARS-Coronavirus Pathogenesis in Mice.

Host genetic variation is known to contribute to differential pathogenesis following infection. Mouse models allow direct assessment of host genetic factors responsible for susceptibility to Severe Acute Respiratory Syndrome coronavirus (SARS-CoV). Based on an assessment of early stage lines from the Collaborative Cross mouse multi-parent population, we identified two lines showing highly divergent susceptibilities to SARS-CoV: the resistant CC003/Unc and the susceptible CC053/Unc.

Novel mutant green fluorescent protein protease substrates reveal the activation of specific caspases during apoptosis.

Background: The caspase-mediated proteolysis of many cellular proteins is a critical event during programmed cell death or apoptosis. It is important to determine which caspases are activated in mammalian cells, and where and when activation occurs, upon receipt of specific death stimuli. Such information would be useful in the design of strategies to regulate the activation of caspases during apoptosis.

Role of ICE-like proteases in endothelial cell hypoxic and reperfusion injury.

Because of its location between blood and tissue, the endothelium is particularly vulnerable to hypoxic/reperfusion injury, but the mechanisms responsible for this injury are not known. A number of recent findings suggest that hypoxia and reperfusion injures neuronal cells via apoptosis. Apoptosis has recently been shown to depend on the activation of a class of proteases with homology to Interleukin-1 beta converting enzyme (ICE) protease.

Contribution of pH-dependent group II phospholipase A2 to chemical hypoxic injury in rat hepatocytes.

Numerous studies have suggested that enhanced membrane phospholipid degradation contributes to hypoxic and ischemic injury. Recently, acidosis has been found to potently protect against hypoxic and ischemic injury. To investigate the interrelationships of these two events in hypoxic injury, we studied the role of a pH-dependent group II phospholipase A2 (PLA2, E.

Down-regulation of HCW9 mRNA in rat hepatocytes during chemical hypoxia involves both transcriptional and posttranscriptional mechanisms.

HCW9 cDNA encodes a rat protein with 95% homology to mouse phospholipase A2 activating protein (PLAP). Its mRNA, which is substantially decreased in rat hepatocytes during chemical hypoxic injury, was found to be expressed in all rat tissues examined, including liver, heart, brain, spleen, lung, skeletal muscle, kidney, and testis. To elucidate the mechanisms responsible for this hypoxia-induced down-regulation of HCW9 mRNA levels, the transcription rate and half-life of HCW9 mRNA were measured.