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- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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- Fricke, Tabea C., et al.
(författare)
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Oxidation of methionine residues activates the high-threshold heat-sensitive ion channel TRPV2
- 2019
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 116:48, s. 24359-24365
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Tidskriftsartikel (refereegranskat)abstract
- Thermosensitive transient receptor potential (TRP) ion channels detect changes in ambient temperature to regulate body temperature and temperature-dependent cellular activity. Rodent orthologs of TRP vanilloid 2 (TRPV2) are activated by nonphysiological heat exceeding 50 °C, and human TRPV2 is heat-insensitive. TRPV2 is required for phagocytic activity of macrophages which are rarely exposed to excessive heat, but what activates TRPV2 in vivo remains elusive. Here we describe the molecular mechanism of an oxidation-induced temperature-dependent gating of TRPV2. While high concentrations of H2O2 induce a modest sensitization of heat-induced inward currents, the oxidant chloramine-T (ChT), ultraviolet A light, and photosensitizing agents producing reactive oxygen species (ROS) activate and sensitize TRPV2. This oxidation-induced activation also occurs in excised inside-out membrane patches, indicating a direct effect on TRPV2. The reducing agent dithiothreitol (DTT) in combination with methionine sulfoxide reductase partially reverses ChT-induced sensitization, and the substitution of the methionine (M) residues M528 and M607 to isoleucine almost abolishes oxidation-induced gating of rat TRPV2. Mass spectrometry on purified rat TRPV2 protein confirms oxidation of these residues. Finally, macrophages generate TRPV2-like heat-induced inward currents upon oxidation and exhibit reduced phagocytosis when exposed to the TRP channel inhibitor ruthenium red (RR) or to DTT. In summary, our data reveal a methionine-dependent redox sensitivity of TRPV2 which may be an important endogenous mechanism for regulation of TRPV2 activity and account for its pivotal role for phagocytosis in macrophages.
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- Salah, Walaa, et al.
(författare)
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Using GIS as a decision making support tool for LEED credits
- 2016. - First
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Ingår i: PLEA 2016 : Cities, Buildings, People: Towards Regenerative Environments - Cities, Buildings, People: Towards Regenerative Environments. ; 3
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Konferensbidrag (refereegranskat)abstract
- Green building rating systems are voluntary tools intended to promote sustainable building process through approaching several environmental issues that include sustainable design parameters related to the construction site and others related to its surrounding context. Decision making software support tools and methods are needed to guide practitioners on minimizing building’s environmental impact especially for early design decisions. Hence, the study shows how Geographic Information Systems (GIS) is used as a decision-making support tool for assessing location and transportation (LT) together with sustainable site (SS) categories for Leadership in Energy and Environmental Design (LEED) green building rating system. The methodology is applied on the 10th of Ramadan city in Egypt; creating land suitability analysis for these two LEED categories. The analysis considers sensitive land protection, high priority development sites, surrounding density and diverse uses, and access to quality transit on the context level. It also analyses lithology type and condition as well as habitat and open spaces protection on the site level. The result shows the potential role of integrating GIS analysis as a tool for site selection credits for LEED rating systems. This allows for more data integration to set a solid base for objective decision making process based on contextual conditions. The method can be generalized and applied in similar contexts in order to attract private investments for green construction especially in new development areas.
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