Two recent publications in Nature Medicine （June 2010） have focused attention on the role ofhypoxia inducible factor HIF-2α in cartilage [1, 2]. Using similar mouse models, both groups provide striking evidence imp...Two recent publications in Nature Medicine （June 2010） have focused attention on the role ofhypoxia inducible factor HIF-2α in cartilage [1, 2]. Using similar mouse models, both groups provide striking evidence implicating HIF-2α in experimentally induced osteoarthritis （OA）. While undoubtedly representing significant advances in the field, care must be taken in interpreting these results, in particular in extrapolating the findings to humans.展开更多
Hypoxic preconditioning refers to the exposure of organisms, systems, organs, tissues or cells to moderate hypoxia/ischemia that results in increased resistance to a subsequent episode of severe hypoxia/ischemia. In t...Hypoxic preconditioning refers to the exposure of organisms, systems, organs, tissues or cells to moderate hypoxia/ischemia that results in increased resistance to a subsequent episode of severe hypoxia/ischemia. In this article, we review recent research based on a mouse model of repeated exposure to autohypoxia. Pre-exposure markedly increases the tolerance to or protection against hypoxic insult, and preserves the cellular structure of the brain. Furthermore, the hippocampal activity amplitude and frequency of electroencephalogram, latency of cortical somatosensory-evoked potential and spinal somatosensory-evoked potential progressively decrease, while spatial learning and memory improve. In the brain, detrimental neurochemicals such as free radicals are down-regulated, while beneficial ones such as adenosine are up-regulated. Also, antihypoxia factor（s） and gene（s） are activated. We propose that the tolerance and protective effects depend on energy conservation and plasticity triggered by exposure to hypoxia via oxygen-sensing transduction pathways and hypoxia-inducible factor-initiated cascades. A potential path for further research is the development of devices and pharma-ceuticals acting on antihypoxia factor（s） and gene（s） for the prevention and treatment of hypoxia and related syndromes.展开更多
The fresh water polyp Hydra belongs to the phylum Cnidaria, which diverged from the metazoan lineage before the appearance of bilaterians. In order to understand the evolution of apoptosis in metazoans, we have begun ...The fresh water polyp Hydra belongs to the phylum Cnidaria, which diverged from the metazoan lineage before the appearance of bilaterians. In order to understand the evolution of apoptosis in metazoans, we have begun to elucidate the molecular cell death machinery in this model organism. Based on ESTs and the whole Hydra genome assembly, we have identified 15 caspases. We show that one is activated during apoptosis, four have characteristics of initiator caspases with N-terminal DED, CARD or DD domain and two undergo autoprocessing in vitro. In addition, we describe seven Bcl-2-1ike and two Bak-like proteins. For most of the Bcl-2 family proteins, we have observed mitochondrial localization. When expressed in mammalian cells, HyBak-like 1 and 2 strongly induced apoptosis. Six of the Bcl-2 family members inhibited apoptosis induced by camptothecin in mammalian ceils with HyBcl-2-1ike 4 showing an especially strong protective effect. This protein also interacted with HyBak-like 1 in a yeast two-hybrid assay. Mutation of the conserved leucine in its BH3 domain abolished both the interaction with HyBak-like 1 and the anti-apoptotic effect. Moreover, we describe novel Hydra BH-3-only proteins. One of these interacted with Bcl-2-1ike 4 and induced apoptosis in mammalian cells. Our data indicate that the evolution of a complex network for cell death regulation arose at the earliest and simplest level of multicellular organization, where it exhibited a substantially higher level of complexity than in the protostome model organisms Caenorhabditis and Drosophila.展开更多
Energy metabolism plays an important role in life survival for species living in high altitude hypoxia condition.Air-breathing organisms require oxygen to create energy.Tibetans are the well-adapted highlanders in Qin...Energy metabolism plays an important role in life survival for species living in high altitude hypoxia condition.Air-breathing organisms require oxygen to create energy.Tibetans are the well-adapted highlanders in Qinghai-Tibetan Plateau.It was thought that different metabolic approaches could lead to different adaptation traits to high altitude hypoxia.Recently identified hypoxia inducible factors pathway regulators,endothelial PAS domain protein1(EPAS1)/HIF-2α and PPARA,were involved in decreasing hemoglobin concentrations in Tibetans.Because EPAS1 and PPARA also modulated the energy metabolism during hypoxia,we hypothesized that positive selected EPAS1 and PPARA genes were also involved in unique energy metabolisms in Tibetans.In this brief review,we take a look into genetic determinations to energy metabolisms for hypoxia adaptations traits in Tibetans and mal-adaptive conditions such as high altitude diseases.展开更多
文摘Two recent publications in Nature Medicine （June 2010） have focused attention on the role ofhypoxia inducible factor HIF-2α in cartilage [1, 2]. Using similar mouse models, both groups provide striking evidence implicating HIF-2α in experimentally induced osteoarthritis （OA）. While undoubtedly representing significant advances in the field, care must be taken in interpreting these results, in particular in extrapolating the findings to humans.
基金supported by grants from the National Natural Science Foundation of China (3967087, 81060212, and 81160244)the Beijing Natural Science Foundation (7962009)+2 种基金the China Postdoctoral Science Foundation (20080430851)the Science Foundation of Shandong Province, China (ZR2010HM029)the Inner Mongolia Science Foundation (2010BS1104)
文摘Hypoxic preconditioning refers to the exposure of organisms, systems, organs, tissues or cells to moderate hypoxia/ischemia that results in increased resistance to a subsequent episode of severe hypoxia/ischemia. In this article, we review recent research based on a mouse model of repeated exposure to autohypoxia. Pre-exposure markedly increases the tolerance to or protection against hypoxic insult, and preserves the cellular structure of the brain. Furthermore, the hippocampal activity amplitude and frequency of electroencephalogram, latency of cortical somatosensory-evoked potential and spinal somatosensory-evoked potential progressively decrease, while spatial learning and memory improve. In the brain, detrimental neurochemicals such as free radicals are down-regulated, while beneficial ones such as adenosine are up-regulated. Also, antihypoxia factor（s） and gene（s） are activated. We propose that the tolerance and protective effects depend on energy conservation and plasticity triggered by exposure to hypoxia via oxygen-sensing transduction pathways and hypoxia-inducible factor-initiated cascades. A potential path for further research is the development of devices and pharma-ceuticals acting on antihypoxia factor（s） and gene（s） for the prevention and treatment of hypoxia and related syndromes.
文摘The fresh water polyp Hydra belongs to the phylum Cnidaria, which diverged from the metazoan lineage before the appearance of bilaterians. In order to understand the evolution of apoptosis in metazoans, we have begun to elucidate the molecular cell death machinery in this model organism. Based on ESTs and the whole Hydra genome assembly, we have identified 15 caspases. We show that one is activated during apoptosis, four have characteristics of initiator caspases with N-terminal DED, CARD or DD domain and two undergo autoprocessing in vitro. In addition, we describe seven Bcl-2-1ike and two Bak-like proteins. For most of the Bcl-2 family proteins, we have observed mitochondrial localization. When expressed in mammalian cells, HyBak-like 1 and 2 strongly induced apoptosis. Six of the Bcl-2 family members inhibited apoptosis induced by camptothecin in mammalian ceils with HyBcl-2-1ike 4 showing an especially strong protective effect. This protein also interacted with HyBak-like 1 in a yeast two-hybrid assay. Mutation of the conserved leucine in its BH3 domain abolished both the interaction with HyBak-like 1 and the anti-apoptotic effect. Moreover, we describe novel Hydra BH-3-only proteins. One of these interacted with Bcl-2-1ike 4 and induced apoptosis in mammalian cells. Our data indicate that the evolution of a complex network for cell death regulation arose at the earliest and simplest level of multicellular organization, where it exhibited a substantially higher level of complexity than in the protostome model organisms Caenorhabditis and Drosophila.
基金supported by the"973"National Basic Research Program(2012CB51820500)National Natural Science Foundation of China(NSFC,31160219,81160243,31160232,81160012)Qinghai University Medical School Youth and Middle Scientist Cultura Project in 2012
文摘Energy metabolism plays an important role in life survival for species living in high altitude hypoxia condition.Air-breathing organisms require oxygen to create energy.Tibetans are the well-adapted highlanders in Qinghai-Tibetan Plateau.It was thought that different metabolic approaches could lead to different adaptation traits to high altitude hypoxia.Recently identified hypoxia inducible factors pathway regulators,endothelial PAS domain protein1(EPAS1)/HIF-2α and PPARA,were involved in decreasing hemoglobin concentrations in Tibetans.Because EPAS1 and PPARA also modulated the energy metabolism during hypoxia,we hypothesized that positive selected EPAS1 and PPARA genes were also involved in unique energy metabolisms in Tibetans.In this brief review,we take a look into genetic determinations to energy metabolisms for hypoxia adaptations traits in Tibetans and mal-adaptive conditions such as high altitude diseases.
