Abstract:
:A key mechanism mediating cellular adaptive responses to hypoxia involves the activity of hypoxia-inducible factor 1 (HIF-1), a transcription factor composed of HIF-1α, and HIF-1β subunits. The classical mechanism of regulation of HIF-1 activity involves destabilisation of HIF-1α via oxygen-dependent hydroxylation of proline residues and subsequent proteasomal degradation. Studies from our laboratory revealed that nitric oxide (NO)-mediated activation of cyclic guanosine monophosphate (cGMP) signalling inhibits the acquisition of hypoxia-induced malignant phenotypes in tumour cells. The present study aimed to elucidate a mechanism of HIF-1 regulation involving NO/cGMP signalling. Using human DU145 prostate cancer cells, we assessed the effect of the NO mimetic glyceryl trinitrate (GTN) and the cGMP analogue 8-Bromo-cGMP on hypoxic accumulation of HIF-1α. Concentrations of GTN known to primarily activate the NO/cGMP pathway (100 nM-1 µM) inhibited hypoxia-induced HIF-1α protein accumulation in a time-dependent manner. Incubation with 8-Bromo-cGMP (1 nM-10 µM) also attenuated HIF-1α accumulation, while levels of HIF-1α mRNA remained unaltered by exposure to GTN or 8-Bromo-cGMP. Furthermore, treatment of cells with the calpain (Ca2+-activated proteinase) inhibitor calpastatin attenuated the effects of GTN and 8-Bromo-cGMP on HIF-1α accumulation. However, since calpain activity was not affected by incubation of DU145 cells with various concentrations of GTN or 8-Bromo-cGMP (10 nM or 1 µM) under hypoxic or well-oxygenated conditions, it is unlikely that NO/cGMP signalling inhibits HIF-1α accumulation via regulation of calpain activity. These findings provide evidence for a role of NO/cGMP signalling in the regulation of HIF-1α, and hence HIF-1-mediated hypoxic responses, via a mechanism dependent on calpain.
journal_name
Biosci Repjournal_title
Bioscience reportsauthors
Kim J,Barsoum IB,Loh H,Paré JF,Siemens DR,Graham CHdoi
10.1042/BSR20192345subject
Has Abstractpub_date
2020-01-31 00:00:00issue
1eissn
0144-8463issn
1573-4935pii
221809journal_volume
40pub_type
杂志文章abstract::Background: The present study aimed to evaluate serum 25-hydroxy vitamin D (25(OH) D) levels in Chinese patients with idiopathic benign paroxysmal positional vertigo (BPPV) and to investigate the possible relationship between the occurrence and recurrence of idiopathic BPPV and low 25(OH) D levels. Methods: Between 1 ...
journal_title:Bioscience reports
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abstract::Even though red blood cell (RBC) vesiculation is a well-documented phenomenon, notably in the context of RBC aging and blood transfusion, the exact signalling pathways and kinases involved in this process remain largely unknown. We have established a screening method for RBC vesicle shedding using the Ca(2+) ionophore...
journal_title:Bioscience reports
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journal_title:Bioscience reports
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journal_title:Bioscience reports
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journal_title:Bioscience reports
pub_type: 杂志文章,评审
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journal_title:Bioscience reports
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journal_title:Bioscience reports
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doi:10.1042/BSR20070039
更新日期:2008-10-01 00:00:00
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journal_title:Bioscience reports
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更新日期:1982-07-01 00:00:00
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journal_title:Bioscience reports
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journal_title:Bioscience reports
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journal_title:Bioscience reports
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journal_title:Bioscience reports
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journal_title:Bioscience reports
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doi:10.1042/BSR20100026
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journal_title:Bioscience reports
pub_type: 杂志文章
doi:10.1007/BF01119773
更新日期:1987-07-01 00:00:00
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journal_title:Bioscience reports
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pub_type: 杂志文章,meta分析
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journal_title:Bioscience reports
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journal_title:Bioscience reports
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abstract::Previous studies demonstrated that the adaptive response to stressors and inflammatory signals involves the activation of the autonomous [corrected] nervous system. Catecholamines have been shown to modulate the activity of various immune effector cells directly via membrane adrenergic receptors. Here, we investigated...
journal_title:Bioscience reports
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journal_title:Bioscience reports
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journal_title:Bioscience reports
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