Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) contains an active site Cys and is one of the most sensitive cellular enzymes to oxidative inactivation and redox regulation. Here, we show that inactivation by hydrogen peroxide is strongly enhanced in the presence of carbon dioxide/bicarbonate. Inactivation of isolated mammalian GAPDH by H 2 O 2 increased with increasing bicarbonate concentration and was sevenfold faster in 25 mM (physiological) bicarbonate compared with bicarbonate-free buffer of the same pH. H 2 O 2 reacts reversibly with CO 2 to form a more reactive oxidant, peroxymonocarbonate (HCO 4− ), which is most likely responsible for the enhanced inactivation. However, to account for the extent of enhancement, we propose that GAPDH must facilitate formation and/or targeting of HCO 4− to promote its own inactivation. Inactivation of intracellular GAPDH was also strongly enhanced by bicarbonate: treatment of Jurkat cells with 20 µM H 2 O 2 in 25 mM bicarbonate buffer for 5 min caused almost complete GAPDH inactivation, but no loss of activity when bicarbonate was not present. H 2 O 2 -dependent GAPDH inhibition in bicarbonate buffer was observed even in the presence of reduced peroxiredoxin 2 and there was a significant increase in cellular glyceraldehyde-3-phosphate/dihydroxyacetone phosphate. Our results identify an unrecognized role for bicarbonate in enabling H 2 O 2 to influence inactivation of GAPDH and potentially reroute glucose metabolism from glycolysis to the pentose phosphate pathway and NAPDH production. They also demonstrate what could be wider interplay between CO 2 and H 2 O 2 in redox biology and the potential for variations in CO 2 metabolism to influence oxidative responses and redox signaling.
1 December 2018 in Free Radical Biology and Medicine
It is widely assumed that transformative societal action is required to address the world's many sustainability challenges of today. This is especially true in an urban context, since urban sustainability may assist in improving the conditions of the urban environment and the quality of life of humans. Nevertheless, and despite the many advantages that urban sustainability may bring about, there is a need for studies that look at the role that transformative learning may play in influencing it. This study will address this need. It provides an analysis of the subject matter of transformative learning and how it may be practised and experienced in an urban context, thus contributing to urban sustainability in practical terms. It reports on a survey specifically directed to the teaching staff, on the extent to which transformative learning is being deployed in Higher Education Institutions (HEIs) in supporting urban sustainability efforts. In addition, the study ends by listing and presenting examples of approaches, methods, and initiatives in transformative learning within an urban sustainability context, and provides an analysis of its main features and learned lessons. It concludes with some best practices for transformative learning that could assist in designing and implementing urban sustainability teaching at HEIs, on a broader scale. It can be stated that not only can sustainability thought improve the urban conditions, but as the developing world gets further urbanised, sustainability in the urban context specifically becomes a matter of particular relevance.