OSR1-sensitive regulation of Na<sup>+</sup>/H<sup>+</sup> exchanger activity in dendritic cells

Pasham, Venkanna; Rotte, Anand; Yang, Wenting; Zelenak, Christine; Bhandaru, Madhuri; Föller, Michael; Läng, Florian

doi:10.1152/ajpcell.00420.2011

Cited by 12 publications

(13 citation statements)

References 87 publications

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“…In addition OXSR1 is worth mentioning, because it is known to belong to the Ser/Thr kinase family. OXSR1 ( oxidative stress responsive 1) regulates downstream kinases in response to environmental stress and plays a role in ion co-transportation in kidney 24, ROS formation, and migration of dendritic cells 25. OXSR1 is also found in human heart, but relatively little is known about its functional pathways 26.…”

Section: Discussionmentioning

confidence: 99%

Discovery of Candidate Genes for Muscle Traits Based on GWAS Supported by eQTL-analysis

et al. 2014

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Biochemical and biophysical processes that take place in muscle under relaxed and stressed conditions depend on the abundance and activity of gene products of metabolic and structural pathways. In livestock at post-mortem, these muscle properties determine aspects of meat quality and are measurable. The conversion of muscle to meat mimics pathological processes associated with muscle ischemia, injury or damage in humans and it is an economic factor in pork production. Linkage, association, and expression analyses independently contributed to the identification of trait-associated molecular pathways and genes. We aim at providing multiple evidences for the role of specific genes in meat quality by integrating a genome-wide association study (GWAS) for meat quality traits and the detection of eQTL based on trait-correlated expressed genes and trait-associated markers. The GWAS revealed 51 and 200 SNPs significantly associated with meat quality in a crossbred Pietrain×(German Landrace×Large White) (Pi×(GL×LW)) and a purebred German Landrace (GL) population, respectively. Most significant SNPs in Pi×(GL×LW) were located on chromosomes (SSC) 4 and 6. The data of 47,836 eQTLs at a significance level of p<10-5 were used to scale down the number candidate genes located in these regions. These SNPs on SSC4 showed association with expression levels of ZNF704, IMPA1, and OXSR1; SSC6 SNPs were associated with expression of SIGLEC10 and PIH1D1. Most significant SNPs in GL were located on SSC6 and associated with expression levels of PIH1D1, SIGLEC10, TBCB, LOC100518735, KIF1B, LOC100514845, and two unknown genes. The abundance of transcripts of these genes in muscle, in turn, is significantly correlated with meat quality traits. We identified several genes with evidence for their candidacy for meat quality arising from the integrative approach of a genome-wide association study and eQTL analysis.

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Section: Discussionmentioning

confidence: 99%

Discovery of Candidate Genes for Muscle Traits Based on GWAS Supported by eQTL-analysis

et al. 2014

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“…The increase in cytosolic Na + concentrations is further expected to reverse the Na + /Ca 2+ exchanger with increase in [Ca 2+ ] i . Accordingly, the selective inhibitor of Na + /H + exchanger NHE1 cariporide [88][89][90][91][92] indeed blunted the increase in both, [Ca 2+ ] i and annexin V binding. In tumour cells, cariporide may foster apoptosis, an effect in part due to cytosolic acidification [93].…”

Section: Discussionmentioning

confidence: 87%

Triggering of Suicidal Erythrocyte Death by the Antibiotic Ionophore Nigericin

Bissinger

Malik

Bouguerra

et al. 2015

Basic Clin Pharma Tox

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The K + ,H + ionophore and antibiotic nigericin has been shown to trigger apoptosis and is thus considered for the treatment of malignancy. Cellular mechanisms involved include induction of oxidative stress, which is known to activate erythrocytic Ca 2+ -permeable unselective cation channels leading to Ca 2+ entry, increase in cytosolic Ca 2+ activity ([Ca 2+ ] i ) and subsequent stimulation of eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. This study explored whether and how nigericin induces eryptosis. Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, [Ca 2+ ] i from Fluo3 fluorescence, pH i from BCECF fluorescence, ceramide abundance utilizing antibodies and reactive oxygen species (ROS) formation from DCFDA-dependent fluorescence. A 48-hr exposure of human erythrocytes to nigericin significantly increased the percentage of annexin-V-binding cells (0.1-10 nM), significantly decreased forward scatter (0.1-1 nM), significantly decreased cytosolic pH (0.1-1 nM) and significantly increased Fluo3 fluorescence (0.1-10 nM). Nigericin (1 nM) slightly, but significantly, increased ROS, but did not significantly modify ceramide abundance. Materials and MethodsErythrocytes, solutions and chemicals. Li-heparin-anticoagulated fresh blood samples were kindly provided by the blood bank of the University of T€ ubingen. The study was approved by the ethics committee of the University of T€ ubingen (184/2003 V). The blood was centrifuged at 120 9 g for 20 min. at 21°C and the platelet-and leucocyte-containing supernatant were disposed. Erythrocytes were incubated in vitro at a haematocrit of 0.4% in Ringer solution containing (in mM) 125 NaCl, 5 KCl, 1 MgSO 4 , 32 N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid (HEPES; pH 7.4), 5 glucose and 1 CaCl 2 , at 37°C for 48 hr. Where indicated, erythrocytes were exposed to nigericin (Enzo Life Sciences, L€ orrach, Germany) at the indicated concentrations.Annexin V binding and forward scatter. After incubation under the respective experimental condition, a 150-ll cell suspension was centrifuged at 350 rcf for 3 min. and, after trashing the supernatant,

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“…By regulation of ion transport, SPAK contributes to cell volume regulation [24,36]. Most recent observations pointed to a role of OSR1 and/or SPAK in the regulation of Na + coupled phosphate transport [37,38], and Na + /H + exchanger [39], pointing to a broader role of those kinases in the regulation of epithelial transport. To the best of our knowledge, nothing is hitherto known about a role of SPAK in the regulation of peptide transporters.…”

Section: Introductionmentioning

confidence: 99%

SPAK Dependent Regulation of Peptide Transporters PEPT1 and PEPT2

Warsi

Luo

Elvira

et al. 2014

Kidney Blood Press Res

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Background/Aims: SPAK (STE20-related proline/alanine-rich kinase) is a powerful regulator of renal tubular ion transport and blood pressure. Moreover, SPAK contributes to the regulation of cell volume. Little is known, however, about a role of SPAK in the regulation or organic solutes. The present study thus addressed the influence of SPAK on the peptide transporters PEPT1 and PEPT2. Methods: To this end, cRNA encoding PEPT1 or PEPT2 were injected into Xenopus laevis oocytes without or with additional injection of cRNA encoding wild-type, SPAK, WNK1 insensitive inactive ^T233ASPAK, constitutively active ^T233ESPAK, and catalytically inactive ^D212ASPAK. Electrogenic peptide (glycine-glycine) transport was determined by dual electrode voltage clamp and PEPT2 protein abundance in the cell membrane by chemiluminescence. Intestinal electrogenic peptide transport was estimated from peptide induced current in Ussing chamber experiments of jejunal segments isolated from gene targeted mice expressing SPAK resistant to WNK-dependent activation (spak^tg/tg) and respective wild-type mice (spak^+/+). Results: In PEPT1 and in PEPT2 expressing oocytes, but not in oocytes injected with water, the dipeptide gly-gly (2 mM) generated an inward current, which was significantly decreased following coexpression of SPAK. The effect of SPAK on PEPT1 was mimicked by ^T233ESPAK, but not by ^D212ASPAK or ^T233ASPAK. SPAK decreased maximal peptide induced current of PEPT1. Moreover, SPAK decreased carrier protein abundance in the cell membrane of PEPT2 expressing oocytes. In intestinal segments gly-gly generated a current, which was significantly higher in spak^tg/tg than in spak^+/+ mice. Conclusion: SPAK is a powerful regulator of peptide transporters PEPT1 and PEPT2.

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OSR1-sensitive regulation of Na⁺/H⁺ exchanger activity in dendritic cells

Cited by 12 publications

References 87 publications

Discovery of Candidate Genes for Muscle Traits Based on GWAS Supported by eQTL-analysis

Discovery of Candidate Genes for Muscle Traits Based on GWAS Supported by eQTL-analysis

Triggering of Suicidal Erythrocyte Death by the Antibiotic Ionophore Nigericin

SPAK Dependent Regulation of Peptide Transporters PEPT1 and PEPT2

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OSR1-sensitive regulation of Na+/H+ exchanger activity in dendritic cells

Cited by 12 publications

References 87 publications

Discovery of Candidate Genes for Muscle Traits Based on GWAS Supported by eQTL-analysis

Discovery of Candidate Genes for Muscle Traits Based on GWAS Supported by eQTL-analysis

Triggering of Suicidal Erythrocyte Death by the Antibiotic Ionophore Nigericin

SPAK Dependent Regulation of Peptide Transporters PEPT1 and PEPT2

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OSR1-sensitive regulation of Na⁺/H⁺ exchanger activity in dendritic cells