Angiotensin II directly induces muscle protein catabolism through the ubiquitin-proteasome proteolytic pathway and may play a role in cancer cachexia

The ability of angiotensin I (Ang I) and II (Ang II) to induce directly protein degradation in skeletal muscle has been studied in murine myotubes. Angiotensin I stimulated protein degradation with a parabolic dose-response curve and with a maximal effect between 0.05 and 0.1 μM. The effect was attenuated by coincubation with the angiotensin-converting enzyme (ACE) inhibitor imidaprilat, suggesting that angiotensin I stimulated protein degradation through conversion to Ang II. Angiotensin II also stimulated protein breakdown with a similar dose-response curve, and with a maximal effect between 1 and 2.5 μM. Total protein degradation, induced by both Ang I and Ang II, was attenuated by the proteasome inhibitors lactacystin (5 μM) and MG132 (10 μM), suggesting that the effect was mediated through upregulation of the ubiquitin-proteasome proteolytic pathway. Both Ang I and Ang II stimulated an increased proteasome 'chymotrypsin-like' enzyme activity as well as an increase in protein expression of 20S proteasome α-subunits, the 19S subunits MSSI and p42, at the same concentrations as those inducing protein degradation. The effect of Ang I was attenuated by imidaprilat, confirming that it arose from conversion to Ang II. These results suggest that Ang II stimulates protein degradation in myotubes through induction of the ubiquitin-proteasome pathway. Protein degradation induced by Ang II was inhibited by insulin-like growth factor and by the polyunsaturated fatty acid, eicosapentaenoic acid. These results suggest that Ang II has the potential to cause muscle atrophy through an increase in protein degradation. The highly lipophilic ACE inhibitor imidapril (Vitor™) (30 mg kg-1) attenuated the development of weight loss in mice bearing the MAC16 tumour, suggesting that Ang II may play a role in the development of cachexia in this model. © 2005 Cancer Research.

Negotiating access and establishing expertise

This book is concerned with the day-to-day realities of doing social science research. It is based upon the reflections and experiences of a wide range of established social researchers, the majority of whom undertake research in the field of health care. By drawing upon their anecdotal accounts of setting up research projects, negotiating access, collecting and analysing data, and disseminating findings, the book highlights a multitude of practical and ethical complexities involved in the conduct of empirically based research. It delineates the emotional, social and cultural factors involved at all stages of the research process, and sets this delineation in the context of wider debates about the relationship between research methods and research ethics.

Knowledge management for more sustainable water systems

The management and sharing of complex data, information and knowledge is a fundamental and growing concern in the Water and other Industries for a variety of reasons. For example, risks and uncertainties associated with climate, and other changes require knowledge to prepare for a range of future scenarios and potential extreme events. Formal ways in which knowledge can be established and managed can help deliver efficiencies on acquisition, structuring and filtering to provide only the essential aspects of the knowledge really needed. Ontologies are a key technology for this knowledge management. The construction of ontologies is a considerable overhead on any knowledge management programme. Hence current computer science research is investigating generating ontologies automatically from documents using text mining and natural language techniques. As an example of this, results from application of the Text2Onto tool to stakeholder documents for a project on sustainable water cycle management in new developments are presented. It is concluded that by adopting ontological representations sooner, rather than later in an analytical process, decision makers will be able to make better use of highly knowledgeable systems containing automated services to ensure that sustainability considerations are included. © 2010 The authors.