Lipid peroxidation research
In the field of free radical and oxidative stress research, lipid peroxidation (LPO) has been studied intensively over decades. Starting in the areas of chemistry and food chemistry, lipid peroxidation research shifted to become a hot topic in biological research. It is now widely acknowledged that LPO processes play a role in several diseases and the ageing process. This is based on the effects of LPO on cellular metabolism and cell functioning. Scientific research in the field of LPO started from the dogma that LPO-related processes are always damaging. Current understanding of LPO is more complex and numerous modulatory effects are known which are important for maintaining cellular integrity and adaptive cellular responses.
The work on LPO is focused in particular on the development of analytical methods, the formation rate of various metabolites and, of course, on the suppression of LPO by various antioxidants. However, research in LPO was, until recently, carried out in numerous laboratories that exchanged experience and results, but did not intensively interact and coordinate their research activities. Therefore, a joint initiative was created during the past 4 years within the European Cooperation in the field of Scientific and Technical Research (COST), denoted COST B35 Action ‘Lipid Peroxidation Associated Disorders: LPO’.
The COST initiative ‘Lipid Peroxidation Associated Disorders’ (COST B35 Action, 2006–2010)
In order to increase and disseminate the knowledge on LPO, the COST B35 Action provided a networking research platform aiming to improve the understanding, monitoring and control of LPO in medicine and biomedical research. To achieve these goals more than 200 researchers from 26 European countries, USA, Japan and Canada developed an interdisciplinary network involving 49 research teams (www.irb.hr/costb35). The COST B35 Action was structured according to its scientific objectives in four working groups: (1) Improvement of methods for the determination of LPO products; (2) Studies of the fundamental aspects of LPO; (3) Pathological aspects of LPO; and (4) Development and validation of antioxidants. Researchers involved in these working groups were interacting in their research activities and the entire B35 Action was interacting with complementary COST Actions and professional societies, in particular with the Society of Free Radical Research-Europe (SFRR-E), organizing joint workshops and conferences in 2008 (Berlin) and 2009 (Rome) and a COST B35/SFRR-E joint summer school on ‘Lipid Peroxidation and Free Radical Signalling: Role in Pathophysiology’ in Greece in 2008. Accordingly, even the final conference of COST B35 Action in 2010 (Turin) is a particular attempt of promotion of research on LPO organized jointly with the International 4-Hydroxynonenal Club, an interest group within the SFRR. This conference, denoted ‘Lipid Peroxidation, Human Diseases and Ageing’, involved not only well known experts but in particular young researchers in the field. Quantitatively summarized results of COST B35 Action are given in , while their qualitative scientific highlights are described below.
Table I. Quantitative summary of results of the activities during the 4-year period (2006 – 2010) of COST B35 action lipid peroxidation associated disorders.
The results of the COST action B35 reflect fundamental activity principles of the COST system. The B35 Action was the first European initiative coordinating research in the field of LPO and oxidative stress. Being very successful, COST B35 Action was followed by several COST actions afterwards that interacted fruitfully and served as a base for new research and networking activities in the fields of oxidative stress and alterations of structure and function of major bioactive molecules, in particular molecular biosciences dealing with lipid and protein metabolism.
COST in EUROPE; the benefits of networking in science
So, what is COST under which COST B35 was funded? COST is an inter-governmental framework for European COoperation in Science and Technology (www.cost.eu). It promotes and coordinates nationally-funded research in Europe and thus contributes to reducing the fragmentation in European research investments, while at the same time opening the European research area to cooperation worldwide. Together with EUREKA and the EU FP programmes, COST is one of the three pillars of joint European research initiatives, with COST being the oldest one (since 1971).
COST has nine scientific Domains (), one of which is the Domain of Biomedicine and Molecular Biosciences (BMBS). COST Action B35 was funded under the BMBS Domain, which currently funds a total of 29 Actions. COST is unique in that it invites multi- and inter-disciplinary proposals under the ‘Trans-Domain’ track; proposals scanning across different areas and thus not fitting in a single Domain are submitted in the Trans-Domain track.
Table II. COST scientific domains.
COST provides funds for research networks, called Actions, which form the main COST instrument. A COST Action is a consortium of—mainly—European scientists working on a common research area. Actions are supported for 4 years for networking and dissemination activities, like meetings, exchange visits, publications, dissemination, training, and average funding is 100 kEuros per year per action.
COST is often criticized in that it does not fund research and that its funding is limited. Yet, COST caters for such important aspects of the research environment like networking activities, which remain either non-funded by the research grants or are bound by complex management and pre-determined participations (of the consortia members only). In contrast, a COST action remains dynamic and allows the addition of new members throughout its life span of 4 years and is based on flexible management and fast-track procedures acting as a catalyst to bring scientists together.
A COST action will allow a total of 8–10 large workshops with 60–70 scientists/workshop (also from partners who joined after the start of the action) (on average this translates into up to 600 scientists networking for the lifetime of an action). The continuity of meetings with colleagues over 4 years supports in-depth discussion of scientific matters, creates new cooperations (especially with scientists who join the action after its start) and sustains pre-existing collaborations.
COST action B35 on ‘Lipid peroxidation and associated disorders’, was such an example of a very successful COST Action which attracted more researchers into the field, stimulated and sustained future collaboration of the members and advanced the knowledge on LPO. As a result, the current issue of Free Radical Research serves as the final publication of COST B35, but again we hope that it is also a starting point for new ways in LPO research.
The COST B35 action tribute to the LPO research
The COST B35 action as networking researchinitiative was well aware of the fact that development of LPO was always triggered by the availability of methods. This development started already with early possibilities to detect malondialdehyde (or rather thiobarbituric acid reactive substances) developed by Yagi and colleagues [Citation1,Citation2], and is continued today using a modern repertoire of immunochemistry and MS-based techniques. However, the detection of lipid peroxidation is still not satisfactory, especially the comparison of the results from different laboratories is far from desirable. Therefore, inter-laboratory comparisons, standardizations of methods and distribution of stabilized standards are still on the agenda of LPO research. The publication of Breusing et al. [Citation3] describes the most recent attempt and gives some ideas about current possibilities. Interestingly, out of the standard methods the determination of thiobarbituric acid reactive substances based on HPLC with fluorescence detection seems to be still the most convenient for human plasma samples used in this study [Citation3]. Since all thiobarbituric acid-based tests have serious disadvantages, the search for new methods is important for the exact evaluation of LPO related processes. As Spickett et al. [Citation4] point out, there are two principal ways to go: (i) the use of new methods (GS-MS, ELISA-based, etc.) and (ii) the identification and detection of more specific, stable products of LPO (oxysterols, isoprostanes, etc.). Interestingly, this approach was already undertaken for the first time many years ago, by analysing the complex spectrum of fatty acid oxidation products in the early 1960s. This led to the discovery of 4-hydroxynonenal (HNE) in 1962 by Schauenstein and Esterbauer. Since then, much work has been performed to study the formation, the effects and the detoxification of this compound. The focusing on HNE led to the impression that HNE is the only LPO product, but one should not forget that LPO is a complex process accompanied by oxidative degradation of many cellular lipids and the formation of a whole array of products. However, the effects of LPO are not limited to the ‘pure’ chemical formation. Numerous enzymes are able to transform LPO products, secondary metabolites are formed and some of these have a more damaging effect when compared to the original LPO products. Knowledge on the chemistry and biochemistry of LPO is summarized by Guéraud et al. [Citation5]. Highlighting hot research topics on biotransformation, modification of macromolecules and signalling effects, this review gives an excellent overview.
Many, if not all, of these products influence cellular metabolism and are contributing eventually to pathological processes, as reviewed by Negre-Salvayre et al. [Citation6]. Evidence is given that LPO takes part in neurodegenerative diseases, in atherosclerosis, diabetes, cancer, inflammatory diseases and finally in the ageing process itself. Since it is well-established that over-production of LPO products will have pathological consequences, the suppression of unwanted LPO to reduce the load with LPO products is a major research field. New natural and synthetic antioxidants are used to achieve the desired effects and target these compounds to their site of action. LPO is clearly not only a pathological but also a physiological process for various cells and tissues. Therefore, antioxidants may be considered as biological stress–response modifiers interacting with cellular components during homeostasis and hormesis. This is reviewed by Augustyniak et al. [Citation7].
COST B35 action ‘Lipid peroxidation and associated disorders’ was attracting many new researchers into LPO research. Therefore, the current issue on Free Radical Research is formally the final publication of COST B35 action, but it is hopefully also a starting point for new ways in LPO research and scientific and technological collaborations.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
This paper was first published online on Early Online on 16 July 2010.
References
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- Yagi K. Assay for blood plasma or serum. Methods Enzymol 1984;105:328–331.
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