The role of calcium in hypoxia-induced signal transduction and gene expression.
ABSTRACT Mammalian cells require a constant supply of oxygen in order to maintain adequate energy production, which is essential for maintaining normal function and for ensuring cell survival. Sustained hypoxia can result in cell death. Sophisticated mechanisms have therefore evolved which allow cells to respond and adapt to hypoxia. Specialized oxygen-sensing cells have the ability to detect changes in oxygen tension and transduce this signal into organ system functions that enhance the delivery of oxygen to tissue in a wide variety of different organisms. An increase in intracellular calcium levels is a primary response of many cell types to hypoxia/ischemia. The response to hypoxia is complex and involves the regulation of multiple signaling pathways and coordinated expression of perhaps hundreds of genes. This review discusses the role of calcium in hypoxia-induced regulation of signal transduction pathways and gene expression. An understanding of the molecular events initiated by changes in intracellular calcium will lead to the development of therapeutic approaches toward the treatment of hypoxic/ischemic diseases and tumors.
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ABSTRACT: Preeclampsia is a pregnancy-specific disease characterized by hypertension, proteinuria, and oxidative stress in the placenta. During the last trimester of gestation, calcium (Ca(2+)) transport from mother to fetus increases dramatically in response to the increased demand for Ca(2+) caused by bone mineralization in the fetus. Ca(2+) supplementation can significantly reduce the incidence and severity of preeclampsia or delay its onset. Ca(2+) transport channels (CTCs) include transient receptor potential vanilloid 6 (TRPV6), plasma membrane Ca(2+) ATPase (PMCA1), and Na(+)/Ca(2+) exchangers (NCKX3 or NCX1). We hypothesized that trans-placental Ca(2+) exchange in preeclamptic trophoblasts may be compensated for successful fetal bone mineralization. The roles of cell membrane channels (TRPV6, PMCA1, NCKX3 and NCX1) were examined in placental primary cells and in normotensive and preeclamptic placentas. The biomarker gene for preeclampsia, soluble fms-like tyrosine kinase-1 (sFLT1) or marker for oxygen-sensitive gene, hypoxia-sensitive inducible factor 1α (HIF-1α), were up-regulated in the preeclamptic placentas and hypoxic cells. The detection of sFLT1 and HIF-1α genes demonstrated that our experimental conditions were suitable to verify a preeclamptic condition. In women experiencing preterm labor, CTC expressions was found to be increased in the fetal and maternal regions of the preeclamptic placenta compared to the observed in normotensive placenta. During term labor, TRPV6 and PMCA1 were highly expressed in the fetal and maternal sections of preeclamptic placenta, while the expression of NCKX3 and NCX1 was reduced. In addition, the expression of CTCs was altered in hypoxia-stressed placental cells. Taken together, our findings demonstrated that the expression of CTCs was regulated by hypoxia stress in placenta tissues and cells, suggesting that our experimental in vitro hypoxic conditions were similar to those of preeclampsia. Furthermore, impaired Ca(2+) metabolism found in preeclamptic syncytiotrophoblasts was resulted from hypoxic stress, which may induce expression of Ca(2+) transport proteins in the placenta to maintain the balance between maternal and fetal Ca(2+) demand during pregnancy.Molecular and Cellular Endocrinology 12/2012; 367(1-2). DOI:10.1016/j.mce.2012.12.012 · 4.24 Impact Factor
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ABSTRACT: Soil flooding is an environmental constraint that is increasingly important for forest ecosystems, affecting tree growth and regeneration. As a result, selection pressure will alter forest diversity and distribution by favouring tree species tolerant of soil oxygen deprivation. Sessile and pedunculate oaks are the most abundant oak species and they exhibit a strong differential tolerance to waterlogging. In order to gain some understanding of the mechanisms of tolerance of both species to hypoxia, we undertook the characterization of the physiological, morphological, cellular and molecular responses of both species to flooding stress. Our results indicate that pedunculate oak, the more tolerant species, succeeded in maintaining its growth, water status and photosynthetic activity at a higher level than sessile oak. Furthermore, pedunculate oak developed aerenchyma in its root cortex as well as adventitious roots. The later exhibited a strong accumulation of class1 non-symbiotic haemoglobin localized by in situ hybridization in the protoderm and in some cortical cells. In conclusion, the higher tolerance of pedunculate oak to flooding was associated with an enhanced capacity to maintain photosynthesis and water homeostasis, coupled with the development of adaptive features (aerenchyma, adventitious roots) and with a higher expression of non-symbiotic haemoglobin in the roots.Plant Cell and Environment 03/2011; 34(7):1113-26. DOI:10.1111/j.1365-3040.2011.02309.x · 5.91 Impact Factor
- Cell Calcium 06/2005; 37(5):371-4. DOI:10.1016/j.ceca.2005.01.004 · 4.21 Impact Factor