The alpha class glutathione s-transferase (GST) isozyme GSTA4-4 (EC2.5.1.18) exhibits high catalytic efficiency towards 4-hydroxynon-2-enal (4-HNE), a major end product of oxidative stress induced lipid peroxidation. ...The alpha class glutathione s-transferase (GST) isozyme GSTA4-4 (EC2.5.1.18) exhibits high catalytic efficiency towards 4-hydroxynon-2-enal (4-HNE), a major end product of oxidative stress induced lipid peroxidation. Exposure of cells and tissues to heat, radiation, and chemicals has been shown to induce oxidative stress resulting in elevated concentrations of 4-HNE that can be detrimental to cell survival. Alternatively, at physiological levels 4-HNE acts as a signaling molecule conveying the occurrence of oxidative events initiating the activation of adaptive pathways. To examine the impact of oxidative/electrophilic stress in a model with impaired 4-HNE metabolizing capability, we disrupted the Gsta4 gene that encodes GSTA4-4 inmice. The effect of electrophile and oxidants on embryonic fibroblasts (MEF) isolated from wild type (WT) and Gsta4 null mice were examined. Results indicate that in the absence of GSTA4-4, oxidant-induced toxicity is potentiated and correlates with elevated accumulation of 4-HNE adducts and DNA damage. Treatment of Gsta4 null MEF with 1,1,4-tris(acetyloxy)-2(E)-nonene [4-HNE(Ac)3], a pro-drug form of 4-HNE, resulted in the activation and phosphorylation of the c-jun-N-terminal kinase (JNK), extracellular-signal-regulated kinases (ERK 1/2) and p38 mitogen activated protein kinases (p38 MAPK) accompanied by enhanced cleavage of caspase-3. Interestingly, when recombinant mammalian or invertebrate GSTs were delivered to Gsta4 null MEF, activation of stress-related kinases in 4-HNE(Ac)3 treated Gsta4 null MEF were inversely correlated with the catalytic efficiency of delivered GSTs towards 4-HNE. Our data suggest that GSTA4-4 plays a major role in protecting cells from the toxic effects of oxidant chemicals by attenuating the accumulation of 4-HNE.展开更多
Floods are the most widespread climate-related hazards in the world, and they impact more people globally than any other type of natural disasters. It causes over one third of the total economic loss from natural cata...Floods are the most widespread climate-related hazards in the world, and they impact more people globally than any other type of natural disasters. It causes over one third of the total economic loss from natural catastrophes and is responsible for two thirds of people affected by natural disasters. On the other hand, studies and analysis have shown that damage reductions due to forecasts improvements can range from a few percentage points to as much as 35% of annual flood damages. About 300 people lose their lives each year due to floods and landslides in Nepal with property damage exceeding 626 million NPR on average. The West Rapti River basin is one of the most flood prone river basins in Nepal. The real-time flood early warning system together with the development of water management and flood protection schemes plays a crucial role in reducing the loss of lives and properties and in overall development of the basin. The non-structural mitigating measure places people away from flood. This method is designed to reduce the impact of flooding to society and economy. This paper presents an overview of flood problems in the West Rapti River basin, causes and consequences of recent floods and the applicability and effectiveness of the real time data to flood early warning in Nepal.展开更多
文摘The alpha class glutathione s-transferase (GST) isozyme GSTA4-4 (EC2.5.1.18) exhibits high catalytic efficiency towards 4-hydroxynon-2-enal (4-HNE), a major end product of oxidative stress induced lipid peroxidation. Exposure of cells and tissues to heat, radiation, and chemicals has been shown to induce oxidative stress resulting in elevated concentrations of 4-HNE that can be detrimental to cell survival. Alternatively, at physiological levels 4-HNE acts as a signaling molecule conveying the occurrence of oxidative events initiating the activation of adaptive pathways. To examine the impact of oxidative/electrophilic stress in a model with impaired 4-HNE metabolizing capability, we disrupted the Gsta4 gene that encodes GSTA4-4 inmice. The effect of electrophile and oxidants on embryonic fibroblasts (MEF) isolated from wild type (WT) and Gsta4 null mice were examined. Results indicate that in the absence of GSTA4-4, oxidant-induced toxicity is potentiated and correlates with elevated accumulation of 4-HNE adducts and DNA damage. Treatment of Gsta4 null MEF with 1,1,4-tris(acetyloxy)-2(E)-nonene [4-HNE(Ac)3], a pro-drug form of 4-HNE, resulted in the activation and phosphorylation of the c-jun-N-terminal kinase (JNK), extracellular-signal-regulated kinases (ERK 1/2) and p38 mitogen activated protein kinases (p38 MAPK) accompanied by enhanced cleavage of caspase-3. Interestingly, when recombinant mammalian or invertebrate GSTs were delivered to Gsta4 null MEF, activation of stress-related kinases in 4-HNE(Ac)3 treated Gsta4 null MEF were inversely correlated with the catalytic efficiency of delivered GSTs towards 4-HNE. Our data suggest that GSTA4-4 plays a major role in protecting cells from the toxic effects of oxidant chemicals by attenuating the accumulation of 4-HNE.
文摘Floods are the most widespread climate-related hazards in the world, and they impact more people globally than any other type of natural disasters. It causes over one third of the total economic loss from natural catastrophes and is responsible for two thirds of people affected by natural disasters. On the other hand, studies and analysis have shown that damage reductions due to forecasts improvements can range from a few percentage points to as much as 35% of annual flood damages. About 300 people lose their lives each year due to floods and landslides in Nepal with property damage exceeding 626 million NPR on average. The West Rapti River basin is one of the most flood prone river basins in Nepal. The real-time flood early warning system together with the development of water management and flood protection schemes plays a crucial role in reducing the loss of lives and properties and in overall development of the basin. The non-structural mitigating measure places people away from flood. This method is designed to reduce the impact of flooding to society and economy. This paper presents an overview of flood problems in the West Rapti River basin, causes and consequences of recent floods and the applicability and effectiveness of the real time data to flood early warning in Nepal.
