Modulation of expression of Na<sup>+</sup>/Ca<sup>2+</sup> exchanger in heart of rat and mouse under stress

Hudecová, Soňa; Kubovčáková, Lucia; Květňanský, Richard; Kopáček, Juraj; Pastoreková, Silvia; Novàkovâ, Marie; Knézl, V.; Tarabová, Bohumila; Lacinová, Ľubica; Sulová, Zdena; Breier, Albert; Jurkovičová, Dana; Križanová, Oľga

doi:10.1111/j.1748-1716.2007.01673.x

Cited by 17 publications

(10 citation statements)

References 37 publications

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“…Wash-out of DMOG for 3 hours did not result in a reduction of the NCX1 mRNA and protein to original, control levels, although pH returned to control values. Our results are in agreement with our previous studies (Hudecova et al 2007), where we observed significant increase in NCX1 mRNA and protein in hypoxic cardiomyocytes. Moreover, upregulation of the NCX1 expression and activity observed in microglia after permanent middle cerebral artery occlusion suggests a relevant role of NCX1 in modulating microglia functions in the postischemic brain (Boscia et al 2009).…”

Section: Discussionsupporting

confidence: 94%

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Chemically mimicked hypoxia modulates gene expression and protein levels of the sodium calcium exchanger in HEK 293 cell line via HIF-1α

Hudecová

Lencesova²,

Csáderová³

et al. 2011

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Up to now a little is known about the effect of hypoxia on the sodium calcium exchanger type 1 (NCX1) expression and function. Therefore, we studied how dimethyloxallyl glycine (DMOG), an activator and stabilizer of the hypoxia-inducible factor (HIF)-1α, could affect expression of the NCX1 in HEK 293 cell line. We also tried to determine whether this activation can result in the induction of apoptosis in HEK 293 cells. We have found that DMOG treatment for 3 hours significantly increased gene expression and also protein levels of the NCX1. This increase was accompanied by a decrease in intracellular pH. Wash-out of DMOG did not result in reduction of the NCX1 mRNA and protein to original - control levels, although pH returned to physiological values. Using luciferase reporter assay we observed increase in the NCX1 promoter activity after DMOG treatment and using wild-type mouse embryonic fibroblast (MEF)-HIF-1(+/+) and HIF-1-deficient MEF-HIF-1(-/-) cells we have clearly shown that in the promoter region, HIF-1α is involved in DMOG induced upregulation of the NCX1. Moreover, we also showed that an increase in the NCX1 mRNA due to the apoptosis induction is not regulated by HIF-1α.

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Section: Discussionsupporting

confidence: 94%

“…In our previous studies we have shown that short-term hypoxia (8% oxygen for 6 hours) significantly increased gene expression and protein levels of the NCX1 in rat cardiomyocytes (Hudecova et al 2007). Hypoxia is a state of insufficient oxygen supply of the tissue or cell.…”

Section: Introductionmentioning

confidence: 96%

Chemically mimicked hypoxia modulates gene expression and protein levels of the sodium calcium exchanger in HEK 293 cell line via HIF-1α

Hudecová

Lencesova²,

Csáderová³

et al. 2011

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“…However, sustained stress also inhibits NCX1 activity, an effect that requires corticosteroid release in concert with adrenergic activation. 36 Reversible protein phosphorylation is essential for excitation-contraction coupling, Ca 2+ handling, cell metabolism, myofilament regulation, and cell-cell communication. 37 ~90% of dephosphorylation events are catalysed by just three phosphatases: PP1, PP2A and PP2B (calcineurin), all of which are regulated by microRNA we identified as changing after surgery.…”

Section: Discussionmentioning

confidence: 99%

microRNA signatures of perioperative myocardial injury after elective non-cardiac surgery: prospective observational cohort study

May

Abbott

Arroyo

et al. 2020

Preprint

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Background: Elevated plasma/serum troponin, indicating perioperative myocardial injury (PMI), is common after non-cardiac surgery. However, underlying mechanisms remain unclear. Acute coronary syndrome (ACS) is associated with the early appearance of circulating microRNAs, which regulate post-translational gene expression. We hypothesised that if PMI and ACS share pathophysiological mechanisms, common microRNA signatures should be evident. Methods: Nested case-control study of samples obtained before and after non-cardiac surgery from patients enrolled in two prospective observational studies of PMI (postoperative troponin I/T>99th centile). In cohort one, serum microRNAs were compared between patients with/without PMI, matched for age, gender and comorbidity. Real-time polymerase chain reaction quantified relative microRNA expression (cycle quantification threshold <37) before and after surgery for microRNA signatures associated with ACS, blinded to PMI. In cohort two, we analysed (EdgeR) microRNA from plasma extracellular vesicles using next-generation sequencing (Illumina HiSeq500). microRNA-messenger RNA-function pathway analysis was performed (DIANA miRPath v3.0/TopGO). Results: MicroRNA were detectable in all 59 patients (median age:67yrs (61-75); 42% male), who had similar clinical characteristics independent of developing PMI. In cohort one, PMI was not associated with increased serum microRNA expression levels after surgery (hsa-miR-1-3p mean fold-change (FC): 3.99 (95%CI:1.95-8.19); hsa-miR-133-3p FC:5.67(95%CI:2.94-10.91); p<0.001). hsa-miR-208b-3p was more commonly detected after PMI (odd ratio (OR):10.0 (95%CI:1.9-52.6); p<0.01). Bioinformatic analysis of differentially expressed microRNAs from cohorts one and two identified pathways associated with adrenergic stress involving calcium dysregulation, rather than ischaemia. Conclusions: Circulating microRNAs synonymous with cardiac ischaemia were universally elevated in patients after surgery, independent of developing myocardial injury.

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“…Hypoxia activates the L-type calcium channels in pulmonary vasculature (Weir and Olschewski 2006). Also, hypoxia significantly increases gene expression and also protein levels of the sodium-calcium exchanger type 1 (NCX1) in the rat cardiomyocytes (Hudecova et al 2007) and in human embryonic kidney (HEK 293) cell line (Hudecova et al 2011), probably through the HIF-1α. NCX1 plays a key role in inducing apoptosis after hypoxia in cultured guinea pig ventricular myocytes (Eigel et al 2004).…”

Section: Ip 3 Receptors and Stressmentioning

confidence: 99%

IP3 receptors, stress and apoptosis

Lencesova¹,

Križanová²

2012

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Abstract. Inositol 1,4,5-trisphosphate (IP 3 ) receptors are intracellular calcium channels that are able to release calcium from intracellular stores upon activation by IP 3 and modulation by calcium. IP 3 receptors are involved in variety of processes during physiological, but also in the pathophysiological states. Unraveling their regulation and function, especially under the pathological situations can result in a development of new therapeutic strategies based on the IP 3 receptor´s activation and/or blocking. To the stimuli that can modulate IP 3 receptors belong several stress factors (e.g. immobilization stress, oxidative stress and hypoxia) and also apoptosis. Depending on the length and strength of the stress stimulus, expression of IP 3 receptors can be increased, or decreased. Therefore, in this minireview modulation of IP 3 receptors by some stressors is discussed. Since it was already shown that strong hypoxia might lead to the apoptosis induction, special focus will be given to the hypoxic stress and induction of apoptosis.

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Modulation of expression of Na⁺/Ca²⁺ exchanger in heart of rat and mouse under stress

Cited by 17 publications

References 37 publications

Chemically mimicked hypoxia modulates gene expression and protein levels of the sodium calcium exchanger in HEK 293 cell line via HIF-1α

Chemically mimicked hypoxia modulates gene expression and protein levels of the sodium calcium exchanger in HEK 293 cell line via HIF-1α

microRNA signatures of perioperative myocardial injury after elective non-cardiac surgery: prospective observational cohort study

IP3 receptors, stress and apoptosis

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Modulation of expression of Na+/Ca2+ exchanger in heart of rat and mouse under stress

Cited by 17 publications

References 37 publications

Chemically mimicked hypoxia modulates gene expression and protein levels of the sodium calcium exchanger in HEK 293 cell line via HIF-1α

Chemically mimicked hypoxia modulates gene expression and protein levels of the sodium calcium exchanger in HEK 293 cell line via HIF-1α

microRNA signatures of perioperative myocardial injury after elective non-cardiac surgery: prospective observational cohort study

IP3 receptors, stress and apoptosis

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Modulation of expression of Na⁺/Ca²⁺ exchanger in heart of rat and mouse under stress