FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2593016003> ?p ?o ?g. }

• W2593016003 endingPage "3614" @default.
• W2593016003 startingPage "3614" @default.
• W2593016003 abstract "Abstract Background: Na/H exchanger 1 (NHE1), an important participant in the precise regulation system of intracellular pH (pHi), is known to be involved in pathological processes such as cell transformation, maintenance and active progression of the neoplastic process. Some studies have showed that leukemic cells showed higher pHi than normal cells, and NHE1 inhibitor could induce acidification and apoptosis of the leukemic cells. In this study, we tried to elucidate the role of NHE1 in leukemic cells according to cytarabine (AraC) resistance. Materials and Methods: Two human AML cell lines, AraC sensitive (AS)-OCI-AML2 cells and AraC resistant (AR)-OCI-AML2 cells, primary leukemic cells from AML patients, and normal bone marrow mononuclear cells (BMMNC) from healthy donor were analyzed. The pH-sensitive fluorescent dye, 2′,7′-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) was used to measure pHi and NHE1 activity. The fluorescent ratio of the 490/440 nm was calibrated intracellularly. The expression of NHE1 was measured by qRT-PCR and western blot analysis. To inhibit the NHE1, the amiloride analogue, 5-(N,N-hexamethylene) amiloride (HMA) (10 µM, 20 µM, 30 µM) was used. Results: To confirmed AraC sensitivity, cell lines were treated with 10 µM AraC for 24 hours, and apoptosis fraction in AS-OCI-AML2 cells and AR-OCI-AML2 cells were 53.1±7.2 % and 4.0±0.8 %, respectively. The pHi of AR-OCI-AML2 cells was significantly higher than AS-OCI-AML2 cells (7.839±0.033 vs. 7.589±0.129, P=0.045) and BMMNC (7.839±0.033 vs. 7.578±0.035, P=0.083), and these differences were associated with higher NHE1 activity. Compared AS-OCI-AML2 cells, AR-OCI-AML2 cells showed significantly higher NHE1 expression by western blot analysis (Figure 1), and NHE1 mRNA levels (0.039±0.014 vs. 1.565±0.070, P<.001) by qRT-PCR. Treatment with HMA (20 µM) could induce apoptosis both on AS-OCI-AML2 cells (26.9±2.8%) and AR-OCI-AML2 cells (37.4±18.8%). Interestingly, induction of apoptosis by HMA was dose-dependent both in AS-OCI-AML2 cells and AR-OCI-AML2 cells, and higher concentration of HMA (30 µM) could induce apoptosis on most of AR-OCI-AML2 cells (68.7±20.2%). Co-treatment experiment with 10 µM AraC and 20 µM HMA in AS-OCI-AML2 cells showed additive effect on inducing apoptosis (AraC vs. HMA vs. HMA+AraC = 53.1±12.4 vs. 53.1±12.4 vs. 67.20±4.3%, Figure 2), but in AR-OCI-AML2 cells, co-treatment did not show additional or synergistic effect on inducing apoptosis (AraC vs. HMA vs. HMA+AraC = 4.0±0.1 vs. 27.1±2.2 vs. 28.1±2.0%, Figure 2). As in the cell lines, primary leukemia cells from patients with AraC resistance showing higher pHi and NHE activity than those from patients without. HMA could induce apoptosis on primary cell lines regardless AraC sensitivity. Conclusions: In this study, we first showed that NHE1 inhibition could induce apoptosis in leukemia cells regardless AraC sensitivity. Apoptotic activity was related with higher pHi and NHE activity in AraC resistant cell lines and primary leukemic cells. NHE inhibition induced apoptosis may be independent with AraC induced apoptosis. The heterogeneity in pHi and NHE activity within leukemic cells may be related to alteration in drug delivery machinery or dormant status of leukemia cells. Further experimental and clinical studies are needed to elucidate the therapeutic application of NHE1 inhibitor to AraC resistant AML. Figure 1. Western blot analysis showed higher level of expression of Na/H exchanger I in AR-AML-OCI2 cells than AS-AML-OCI2 cells. Figure 1. Western blot analysis showed higher level of expression of Na/H exchanger I in AR-AML-OCI2 cells than AS-AML-OCI2 cells. Figure 2. Percentage of apoptotic cells after treatment with 20 µM HMA and/or 10 µM AraC. Figure 2. Percentage of apoptotic cells after treatment with 20 µM HMA and/or 10 µM AraC. Disclosures No relevant conflicts of interest to declare." @default.
• W2593016003 created "2017-03-16" @default.
• W2593016003 creator A5003126278 @default.
• W2593016003 creator A5017165636 @default.
• W2593016003 creator A5035241076 @default.
• W2593016003 creator A5039335852 @default.
• W2593016003 creator A5051822919 @default.
• W2593016003 creator A5063101533 @default.
• W2593016003 creator A5063511808 @default.
• W2593016003 creator A5069186788 @default.
• W2593016003 date "2014-12-06" @default.
• W2593016003 modified "2023-10-09" @default.
• W2593016003 title "Inhibition of NHE1 Induced Apoptosis in Cytarabine Resistant Leukemia Cell Lines and Primary Leukemia Cells from AML Patients, Which Showed Increased Intracellular pH and NHE1 Activity" @default.
• W2593016003 doi "https://doi.org/10.1182/blood.v124.21.3614.3614" @default.
• W2593016003 hasPublicationYear "2014" @default.
• W2593016003 type Work @default.
• W2593016003 sameAs 2593016003 @default.
• W2593016003 citedByCount "1" @default.
• W2593016003 countsByYear W25930160032020 @default.
• W2593016003 crossrefType "journal-article" @default.
• W2593016003 hasAuthorship W2593016003A5003126278 @default.
• W2593016003 hasAuthorship W2593016003A5017165636 @default.
• W2593016003 hasAuthorship W2593016003A5035241076 @default.
• W2593016003 hasAuthorship W2593016003A5039335852 @default.
• W2593016003 hasAuthorship W2593016003A5051822919 @default.
• W2593016003 hasAuthorship W2593016003A5063101533 @default.
• W2593016003 hasAuthorship W2593016003A5063511808 @default.
• W2593016003 hasAuthorship W2593016003A5069186788 @default.
• W2593016003 hasBestOaLocation W25930160031 @default.
• W2593016003 hasConcept C134897140 @default.
• W2593016003 hasConcept C153911025 @default.
• W2593016003 hasConcept C178790620 @default.
• W2593016003 hasConcept C185592680 @default.
• W2593016003 hasConcept C190283241 @default.
• W2593016003 hasConcept C203014093 @default.
• W2593016003 hasConcept C2778041864 @default.
• W2593016003 hasConcept C2778461978 @default.
• W2593016003 hasConcept C2779608910 @default.
• W2593016003 hasConcept C502942594 @default.
• W2593016003 hasConcept C537181965 @default.
• W2593016003 hasConcept C54355233 @default.
• W2593016003 hasConcept C55493867 @default.
• W2593016003 hasConcept C79879829 @default.
• W2593016003 hasConcept C81885089 @default.
• W2593016003 hasConcept C86803240 @default.
• W2593016003 hasConcept C95444343 @default.
• W2593016003 hasConceptScore W2593016003C134897140 @default.
• W2593016003 hasConceptScore W2593016003C153911025 @default.
• W2593016003 hasConceptScore W2593016003C178790620 @default.
• W2593016003 hasConceptScore W2593016003C185592680 @default.
• W2593016003 hasConceptScore W2593016003C190283241 @default.
• W2593016003 hasConceptScore W2593016003C203014093 @default.
• W2593016003 hasConceptScore W2593016003C2778041864 @default.
• W2593016003 hasConceptScore W2593016003C2778461978 @default.
• W2593016003 hasConceptScore W2593016003C2779608910 @default.
• W2593016003 hasConceptScore W2593016003C502942594 @default.
• W2593016003 hasConceptScore W2593016003C537181965 @default.
• W2593016003 hasConceptScore W2593016003C54355233 @default.
• W2593016003 hasConceptScore W2593016003C55493867 @default.
• W2593016003 hasConceptScore W2593016003C79879829 @default.
• W2593016003 hasConceptScore W2593016003C81885089 @default.
• W2593016003 hasConceptScore W2593016003C86803240 @default.
• W2593016003 hasConceptScore W2593016003C95444343 @default.
• W2593016003 hasIssue "21" @default.
• W2593016003 hasLocation W25930160031 @default.
• W2593016003 hasOpenAccess W2593016003 @default.
• W2593016003 hasPrimaryLocation W25930160031 @default.
• W2593016003 hasRelatedWork W2022907030 @default.
• W2593016003 hasRelatedWork W2034016319 @default.
• W2593016003 hasRelatedWork W2056895997 @default.
• W2593016003 hasRelatedWork W2070987854 @default.
• W2593016003 hasRelatedWork W2081315501 @default.
• W2593016003 hasRelatedWork W2163342739 @default.
• W2593016003 hasRelatedWork W2180734910 @default.
• W2593016003 hasRelatedWork W2313775743 @default.
• W2593016003 hasRelatedWork W2394514550 @default.
• W2593016003 hasRelatedWork W4249458258 @default.
• W2593016003 hasVolume "124" @default.
• W2593016003 isParatext "false" @default.
• W2593016003 isRetracted "false" @default.
• W2593016003 magId "2593016003" @default.
• W2593016003 workType "article" @default.