Cellular metabolism is inherently linked to the production of oxidizing by-products, including reactive oxygen species (ROS) hydrogen peroxide (H2O2). When present in excess, H2O2 can damage cellular biomolecules, but when produced in coordinated fashion, it typically serves as a mobile signaling messenger. It is therefore not surprising that cell health critically relies on both low-molecular-weight and enzymatic antioxidant components, which protect from ROS-mediated damage and shape the propagation and duration of ROS signals. This review focuses on H2O2–antioxidant cross talk in the endoplasmic reticulum (ER), which is intimately linked to the process of oxidative protein folding. ER-resident or ER-regulated sources of H2O2 and other ROS, which are subgrouped into constitutive and stimulated sources, are discussed and set into context with the diverse antioxidant mechanisms in the organelle. These include two types of peroxide-reducing enzymes, a high concentration of glutathione derived from the cytosol, and feedback-regulated thiol–disulfide switches, which negatively control the major ER oxidase ER oxidoreductin-1. Finally, new evidence highlighting emerging principles of H2O2-based cues at the ER will likely set a basis for establishing ER redox processes as a major line of future signaling research. A fundamental problem that remains to be solved is the specific, quantitative, time resolved, and targeted detection of H2O2 in the ER and in specialized ER subdomains. 相似文献
Objectives: The occurrence of oxidative stress and endoplasmic reticulum (ER) stress in hepatitis C virus (HCV) infection has been demonstrated and play an important role in liver injury. During viral infection, hepatocytes must handle not only the replication of the virus, but also inflammatory signals generating oxidative stress and damage. Although several mechanisms exist to overcome cellular stress, little attention has been given to the adaptive response of hepatocytes during exposure to multiple noxious triggers.
Methods: In the present study, Huh-7 cells and hepatocytes expressing HCV Core or NS3/4A proteins, both inducers of oxidative and ER stress, were additionally challenged with the superoxide anion generator menadione to mimic external oxidative stress. The production of reactive oxygen species (ROS) as well as the response to oxidative stress and ER stress were investigated.
Results: We demonstrate that hepatocytes diminish oxidative stress through a reduction in ROS production, ER-stress markers (HSPA5 [GRP78], sXBP1) and apoptosis (caspase-3 activity) despite external oxidative stress. Interestingly, the level of the autophagy substrate protein p62 was downregulated together with HCV Core degradation, suggesting that hepatocytes can overcome excess oxidative stress through autophagic degradation of one of the stressors, thereby increasing cell survival.
Duscussion: In conclusion, hepatocytes exposed to direct and indirect oxidative stress inducers are able to cope with cellular stress associated with viral hepatitis and thus promote cell survival. 相似文献
Heatwaves, with increases in day and night time temperatures, are predicted to increase in frequency. We investigated the response of forbs, shrubs, grasses and non‐grass monocotyledons from warm temperate environments in Australia to repeated heatwaves to determine if responses differed with growth form and whether the addition of hot night temperatures influenced the ability of species to grow and acclimate. Plants were subjected to 3, 3‐day heatwaves comprising either hot days and nights or hot days and cool nights, with control plants maintained under cool days and nights. All species were thermotolerant to repeated heatwaves, although two species showed lower biomass under heat treatments, indicating repeated heatwaves influenced function in some, but not all species. While there was evidence of photosynthetic damage in some species, these recovered by the end of the experiment. While grasses and one herb showed some evidence of photosystem acclimation, increases in the threshold temperatures for membrane breakdown only occurred in one shrub. Leaf sacrifice in grasses was significantly increased after repeated heatwaves suggesting that fuel loads in grass communities will increase in the future. These results indicate high resilience for these Australian native warm temperate plants although lower growth rates in some species after heatwaves may result in changes to community composition. 相似文献
The endoplasmic reticulum (ER) is a functionally and morphologically complex cellular organelle largely responsible for a variety of crucial functions, including protein folding, maturation and degradation. Furthermore, the ER plays an essential role in lipid biosynthesis, dynamic Ca2+ storage, and detoxification. Malfunctions in ER‐related processes are responsible for the genesis and progression of many diseases, such as heart failure, cancer, neurodegeneration and metabolic disorders. To fulfill many of its vital functions, the ER relies on a sufficient energy supply in the form of adenosine‐5′‐triphosphate (ATP), the main cellular energy source. Despite landmark discoveries and clarification of the functional principles of ER‐resident proteins and key ER‐related processes, the mechanism underlying ER ATP transport remains somewhat enigmatic. Here we summarize ER‐related ATP‐consuming processes and outline our knowledge about the nature and function of the ER energy supply. 相似文献
Aims
Plants play an important role in ecosystem processes. Functional meaning of trait variation in wide environmental gradients is well known but is scarcely known across narrow gradients. We analyze the variation of morphological, physical and chemical traits of dominant plant species and the potential rates of dry mass loss and N release/immobilization during senesced leaf decomposition of these species across a narrow aridity gradient, and to identify indicative traits useful to set species functional groups sharing decomposition patterns. 相似文献