Analysis of pressure ulcer wound fluid using two-dimensional electrophoresis.

The incidence rate of pressure ulcers in the USA ranges from 0.4% to 38% in acute care settings and from 2.2% to 23.9% in long-term care settings, and their treatment costs are in the billions of dollars yearly. The proteome of wound fluid may contain early indicators or biomarkers associated with healing in pressure ulcers that would enable treatment regimes to be optimised for each individual. Wound fluid was collected from the interior and periphery of 19 chronic pressure ulcers at 15 time points during 42 days for an analysis of protein expression. Proteins were fractionated using two-dimensional polyacrylamide gel electrophoresis. A comparison of the spot distributions indicates a biochemical difference between the interior and the periphery of wounds. Pressure ulcers that healed show a greater number of spots for interior and peripheral locations combined over time when compared with wounds that did not heal. Using this technique, protein S100A9 was identified as a potential biomarker of wound healing. The identification of differences within the proteome of healing versus non healing pressure ulcers could have great significance in the use of current treatments, as well as the development of new therapeutic interventions.

A Drosophila ortholog of the human MRJ modulates polyglutamine toxicity and aggregation.

In the Drosophila eye, proteins with an expanded polyglutamine (polyQ) tract form nuclear and cytoplasmic inclusions and produce cytotoxicity, demonstrated as loss of eye pigmentation and structural integrity. An EP P-element that suppressed the loss of eye pigmentation was inserted 9.7 kb upstream of dmrj, a gene that encodes an ortholog of a brain-enriched cochaperone, the human MRJ (mammalian relative of DnaJ). Despite the large distance between them, quantitative polymerase chain reaction indicated that the EP could overexpress dmrj. In the retina and other neurons, transgenic dMRJ suppressed polyQ toxicity and colocalized with its inclusions. In the photoreceptors, expression of another suppressor with a J domain, dHDJ1, but not dMRJ, prior to expression of expanded polyQs dramatically promoted cytoplasmic aggregation. However, both proteins increased the level of detergent-soluble, monomeric polyQ-expanded proteins. These findings exemplify the functional similarities and differences between J domain proteins in suppressing polyQ toxicity.

The Influence of Superoxide Dismutase and Glutathione Peroxidase Deficiencies on Noise-Induced Hearing Loss in Mice.

One consequence of noise exposure is increased production of reactive oxygen species (ROS), such as superoxide, hydrogen peroxide, and hydroxyl radicals, in the cochlea. ROS can cause oxidative damage to diverse cellular components, including membranes, proteins, and DNA, if they are not "neutralised" by antioxidant defences. Two important enzymes of the cochlear antioxidant defense system are cytosolic copper/zinc superoxide dismutase (SOD1) and selenium-dependent glutathione peroxidase (GPx1). These metalloenzymes work together to regulate ROS production in virtually every cell in the body, and they may be important for limiting cochlear damage associated with aging and acoustic overexposure. In this chapter, we describe a series of experiments using mice with targeted deletions of Sod1 or Gpx1, the mouse genes that code for SOD1 and GPx1, respectively, to study the cellular mechanisms underlying noise-induced hearing loss (NIHL). The results from Sod1 and Gpx1 knockout mice provide insights into the link between endogenous levels of antioxidant enzymes and susceptibility to NIHL.