NRF2 activation reprogrammes defects in oxidative metabolism to restore macrophage function in COPD

Rationale: Chronic obstructive pulmonary disease (COPD) is a disease characterized by persistent airway inflammation and disordered macrophage function. The extent to which alterations in macrophage bioenergetics contribute to impaired antioxidant responses and disease pathogenesis has yet to be fully delineated. Objectives: Through the study of COPD alveolar macrophages (AMs) and peripheral monocyte-derived macrophages (MDMs), we sought to establish if intrinsic defects in core metabolic processes drive macrophage dysfunction and redox imbalance. Methods: AMs and MDMs from donors with COPD and healthy donors underwent functional, metabolic, and transcriptional profiling. Measurements and Main Results: We observed that AMs and MDMs from donors with COPD display a critical depletion in glycolytic- and mitochondrial respiration–derived energy reserves and an overreliance on glycolysis as a source for ATP, resulting in reduced energy status. Defects in oxidative metabolism extend to an impaired redox balance associated with defective expression of the NADPH-generating enzyme, ME1 (malic enzyme 1), a known target of the antioxidant transcription factor NRF2 (nuclear factor erythroid 2–related factor 2). Consequently, selective activation of NRF2 resets the COPD transcriptome, resulting in increased generation of TCA cycle intermediaries, improved energetic status, favorable redox balance, and recovery of macrophage function. Conclusions: In COPD, an inherent loss of metabolic plasticity leads to metabolic exhaustion and reduced redox capacity, which can be rescued by activation of the NRF2 pathway. Targeting these defects, via NRF2 augmentation, may therefore present an attractive therapeutic strategy for the treatment of the aberrant airway inflammation described in COPD

Differential generation of hydrogen peroxide upon exposure to zinc and cadmium in the hyperaccumulating plant specie (Sedum alfredii Hance)*

Sedum alfredii Hance has been identified as zinc (Zn) and cadmium (Cd) co-hyperaccumulator. In this paper the relationships of Zn or Cd hyperaccumulation to the generation and the role of H2O2 in Sedum alfredii H. were examined. The results show that Zn and Cd contents in the shoots of Sedum alfredii H. treated with 1000 μmol/L Zn2+ and/or 200 μmol/L Cd2+ increased linearly within 15 d. Contents of total S, glutathione (GSH) and H2O2 in shoots also increased within 15 d, and then decreased. Total S and GSH contents in shoots were higher under Cd2+ treatment than under Zn2+ treatment. However, reverse trends of H2O2 content in shoots were obtained, in which much higher H2O2 content was observed in Zn2+-treated shoots than in Cd2+-treated shoots. Similarly, the microscopic imaging of H2O2 accumulation in leaves using H2O2 probe technique showed that much higher H2O2 accumulation was observed in the Zn2+-treated leaf than in the Cd2+-treated one. These results suggest that there are different responses in the generation of H2O2 upon exposure to Zn2+ and Cd2+ for the hyperaccumulator Sedum alfredii H. And this is the first report that the generation of H2O2 may play an important role in Zn hyperaccumulation in the leaves. Our results also imply that GSH may play an important role in the detoxification of dissociated Zn/Cd and the generation of H2O2

Phytoextraction: a review on enhanced metal availability and plant accumulation Fitoextração: uma revisão sobre disponibilidade induzida e acumulação de metais em plantas

Phytoextraction has emerged as a novel approach to clean up metal-polluted soils in which plants are used to transfer toxic metals from soils to shoots. This review provides a synthesis of current knowledge on phytoextraction of metals from soils and their accumulation in plants. The objective is to integrate soil-related (root exudates and chemical amendments) and biological advances to suggest research needs and future directions. As far as can be deduced from the literature, it will be some time before phytoextraction may be established as a commercial technology. For chemically-assisted phytoextraction, research has not shown easily biodegradable compounds to overcome the risks associated with the use of EDTA for poorly available metals in soils. On the other hand, significant progress has been made on the physiological and molecular aspects regarding tolerance and phytoaccumulation of metals in plants. A multidisciplinary approach is warranted to make phytoextraction a feasible commercial technology to remediate metal-polluted soils.<br>A fitoextração é uma tecnologia emergente para despoluição de solos contaminados por metais pesados que usa plantas para transferir metais do solo para a parte aérea, a qual pode ser removida da área poluída. Esta revisão apresenta uma síntese do atual conhecimento sobre fitoextração de metais pesados do solo e sua acumulação em plantas. O objetivo é integrar em uma mesma discussão os avanços relacionados à química do solo (exsudação radicular e adição de agentes quelantes para aumentar a absorção) e à biologia (tolerância a metais e melhoramento genético) visando sugerir futuras pesquisas na área. Embora promissor, o atual estado de desenvolvimento da fitoextração ainda não permite estabelecê-la como uma tecnologia comercial. A pesquisa ainda não encontrou agentes quelantes facilmente biodegradáveis que possam substituir o EDTA na solubilização de metais pouco disponíveis em solos. Entretanto, significativos progressos têm sido feitos no entendimento dos mecanismos fisiológicos e moleculares de tolerância e acumulação de metais em plantas. Uma abordagem multidisciplinar dos vários aspectos que envolvem a fitoextração poderá tornar essa tecnologia econômica e ambientalmente viável a médio prazo