The role of calcium in hypoxia-induced signal transduction and gene expression

Department of Genome Science, Genome Research Institute, University of Cincinnati, 2180 E. Galbraith Rd., Cincinnati, OH 45237, USA.
Cell Calcium (Impact Factor: 4.21). 09/2004; 36(3-4):331-40. DOI: 10.1016/j.ceca.2004.02.006
Source: PubMed

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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    • "However, several randomized trials have reported the effective use of various methods to reduce the rate or severity of preeclampsia (Sibai et al., 2005), including Ca 2+ supplementation (Hofmeyr et al., 2007; Belizan et al., 1991). Although two clinical trials evaluating the ability of dietary Ca 2+ supplementation to prevent preeclampsia produced disparate results (Belizan et al., 1991; Levine et al., 1997), increased intracellular Ca 2+ levels have been implicated in the development of cell injury and hypoxic stress (Seta et al., 2004). Furthermore, Ca 2+ entry blockers have been reported to protect against cellular necrosis caused by experimental ischemia in the liver, kidney and other tissues (Peck and Lefer, 1981; Lee and Lum, 1986). "
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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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    • "derlying molecular mechanisms have not been fully demonstrated, it has been reported that nonlethal levels of hypoxia can sometimes lead to the upregulation of cell survival genes and signaling pathways (Seta et al., 2004). Cheng and colleagues (Cheng et al., 2007) reported that hypoxia reduced PQ-induced cellular damage in human corneal endothelial cells. "
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    ABSTRACT: Paraquat (1,1'-dimethyl-4,4'-bipyridinium dichloride; PQ), an effective and widely used herbicide, was commercially introduced in 1962. It is reduced by the electron donor NADPH, and then reduced PQ transfers the electrons to molecular oxygen, resulting in the production of reactive oxygen species (ROS), which are related to cellular toxicity. However, the influence of continuous hypoxia on PQ-induced ROS production has not fully been investigated. We evaluated in vitro the protective effect of continuous hypoxia on PQ-induced cytotoxicity in the human carcinogenic alveolar basal epithelial cell line (A549 cells) by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and live and dead assay, and by measuring lactate dehydrogenase (LDH) release. To elucidate the mechanism underlying this effect, we monitored the immunofluorescence of intracellular ROS and measured malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Continuous hypoxia protected the A549 cells from PQ-induced cytotoxicity. Continuous hypoxia for a period of 24 h significantly reduced intracellular ROS, decreased MDA concentration in the supernatant, and normalized SOD and GPx activities. Continuous hypoxia attenuated PQ-induced cell toxicity in A549 cells. This protective effect might be attributable to the suppression of PQ-induced ROS generation.
    Experimental and Molecular Medicine 07/2011; 43(9):494-500. DOI:10.3858/emm.2011.43.9.056 · 2.46 Impact Factor
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    • "This metabolic change will be accompanied by a general decrease in protein synthesis, except for about 20 ANPs (Drew 1997). The plant response to hypoxia encompasses complex interactions between biochemical and genetic programs in particular a differential expression of several genes (Klok et al. 2002; Seta et al. 2004; Kreuzwieser et al. 2009), which include signal transduction components (Baxter-Burrell et al. 2002; Folzer et al. 2005), enzymes involved in ethylene biosynthesis (Vriezen et al. 1999; Drew, He & Morgan 2000), nitrogen metabolism (Agarwal & Grover 2005), cell wall loosening (Saab & Sachs 1996), a large number of transcription factor families (Bailey-Serres & Chang 2005) as well as ns-Hb (Taylor et al. 1994; Duff, Wittenberg & Hill 1997; Trevaskis et al. 1997; Van Dongen et al. 2008; Parent et al. 2008a). Class 1 ns-Hb can modulate NO levels and thus act as a regulator of the NO response (Dordas et al. 2004; Perazzolli et al. 2004). "
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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
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