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Conference Paper: Iron-overload induces apoptosis in cardiomyocytes and hepatocytes via mitochondrial/caspase-3 pathways

TitleIron-overload induces apoptosis in cardiomyocytes and hepatocytes via mitochondrial/caspase-3 pathways
Authors
Issue Date2008
PublisherAmerican Society of Hematology
Citation
5th Annual Meeting of American Society of Hematology, San Francisco, CA., 6-9 December 2008. In Blood, 2008, v. 112 n. 11, p. 656 How to Cite?
AbstractCardiomyopathy and liver damage due to iron-overload are the major complications in patients with beta-thalassaemia major. Iron-overload may induce apoptosis in cardiomyocytes and hepatic cells, and that TPO may exert protective effect on apoptosis of cardiomyocytes (Circulation, 2006). In this study, we demonstrated firstly that iron induced apoptosis in cardiomyocytes. Using H9C2 cells, we have shown that iron reduced cell viability in a dose-dependent manner (0.003-3 mM) (n=6). By annexin V and PI staining, apoptotic cells were found to be significantly increased after iron treatment (0.3 mM, 72 hrs) (n=6). The expression of active caspase-3 was significantly increased in iron-treated cells. Furthermore, iron treatment increased the proportion of cells containing JC-1 monomers, indicating a trend in the drop of mitochondrial membrane potential (n=6). Secondly, we found that TPO exerted cardio-protective effect on iron-induced apoptosis. H9C2 cells were cultured in the presence of iron (0.3 mM) with or without TPO (5, 10, 20, 50, 100 ng/mL, 72 hrs). The cell viability was significantly increased with the treatment of TPO at 50 ng/mL and 100 ng/mL (n=4). Dot-plot analysis of annexin V/PI staining demonstrated that TPO (50 ng/mL) significantly reduced the population of apoptotic cells (n=6). Incubation with TPO also decreased the iron-induced caspase-3 expression (n=6). Flow cytometric dot-plot analysis of H9C2 cells also showed trends of amelioration of the increase in JC-1 monomers in the iron plus TPO group (n=6). The population of phospho-Akt and Erk1/2 were also significantly increased after treatment by TPO (P<0.05, n=4). Human liver cell line MIHA was also used as a cell model. We showed that iron-overload reduced cell viability in a dose-dependent manner (0.0375-0.6 mM) (n=7). By annexin V and PI staining, apoptotic cells were found to be significantly increased after iron treatment (0.15-0.6 mM) for 72 hrs (n=7). The expression of active caspase-3 was also significantly increased in iron-treated cells (n=5). We also found that TPO exerted proliferation effect on MIHA cell by activation of phospho-Akt. However, MIHA cells were cultured in the presence of iron (0.3 mM) with TPO (50 ng/mL, 72 hrs). The cell viability was not significantly increased with the treatment of TPO (n=5). Dot-plot analysis of annexin V/PI staining did not demonstrated that TPO reduced the population of apoptotic cells induced by iron-overload (n=5). Also, incubation with TPO did not decrease the iron-induced caspase-3 expression in these cells (n=5). Our findings suggest that iron-overload induces apoptosis in cardiomyocytes and hepatocytes via mitochondrial/caspase-3 pathways and that TPO might exert a protective effect on iron-overload induced apoptosis via the activation of Akt and Erk1/2 pathways in cardiomyocytes.
Persistent Identifierhttp://hdl.handle.net/10722/62804
ISSN
2015 Impact Factor: 11.841
2015 SCImago Journal Rankings: 6.395

 

DC FieldValueLanguage
dc.contributor.authorYang, Men_HK
dc.contributor.authorChan, Sen_HK
dc.contributor.authorCheung, YFen_HK
dc.contributor.authorHa, SYen_HK
dc.contributor.authorChan, GCFen_HK
dc.date.accessioned2010-07-13T04:09:31Z-
dc.date.available2010-07-13T04:09:31Z-
dc.date.issued2008en_HK
dc.identifier.citation5th Annual Meeting of American Society of Hematology, San Francisco, CA., 6-9 December 2008. In Blood, 2008, v. 112 n. 11, p. 656en_HK
dc.identifier.issn0006-4971-
dc.identifier.urihttp://hdl.handle.net/10722/62804-
dc.description.abstractCardiomyopathy and liver damage due to iron-overload are the major complications in patients with beta-thalassaemia major. Iron-overload may induce apoptosis in cardiomyocytes and hepatic cells, and that TPO may exert protective effect on apoptosis of cardiomyocytes (Circulation, 2006). In this study, we demonstrated firstly that iron induced apoptosis in cardiomyocytes. Using H9C2 cells, we have shown that iron reduced cell viability in a dose-dependent manner (0.003-3 mM) (n=6). By annexin V and PI staining, apoptotic cells were found to be significantly increased after iron treatment (0.3 mM, 72 hrs) (n=6). The expression of active caspase-3 was significantly increased in iron-treated cells. Furthermore, iron treatment increased the proportion of cells containing JC-1 monomers, indicating a trend in the drop of mitochondrial membrane potential (n=6). Secondly, we found that TPO exerted cardio-protective effect on iron-induced apoptosis. H9C2 cells were cultured in the presence of iron (0.3 mM) with or without TPO (5, 10, 20, 50, 100 ng/mL, 72 hrs). The cell viability was significantly increased with the treatment of TPO at 50 ng/mL and 100 ng/mL (n=4). Dot-plot analysis of annexin V/PI staining demonstrated that TPO (50 ng/mL) significantly reduced the population of apoptotic cells (n=6). Incubation with TPO also decreased the iron-induced caspase-3 expression (n=6). Flow cytometric dot-plot analysis of H9C2 cells also showed trends of amelioration of the increase in JC-1 monomers in the iron plus TPO group (n=6). The population of phospho-Akt and Erk1/2 were also significantly increased after treatment by TPO (P<0.05, n=4). Human liver cell line MIHA was also used as a cell model. We showed that iron-overload reduced cell viability in a dose-dependent manner (0.0375-0.6 mM) (n=7). By annexin V and PI staining, apoptotic cells were found to be significantly increased after iron treatment (0.15-0.6 mM) for 72 hrs (n=7). The expression of active caspase-3 was also significantly increased in iron-treated cells (n=5). We also found that TPO exerted proliferation effect on MIHA cell by activation of phospho-Akt. However, MIHA cells were cultured in the presence of iron (0.3 mM) with TPO (50 ng/mL, 72 hrs). The cell viability was not significantly increased with the treatment of TPO (n=5). Dot-plot analysis of annexin V/PI staining did not demonstrated that TPO reduced the population of apoptotic cells induced by iron-overload (n=5). Also, incubation with TPO did not decrease the iron-induced caspase-3 expression in these cells (n=5). Our findings suggest that iron-overload induces apoptosis in cardiomyocytes and hepatocytes via mitochondrial/caspase-3 pathways and that TPO might exert a protective effect on iron-overload induced apoptosis via the activation of Akt and Erk1/2 pathways in cardiomyocytes.-
dc.languageengen_HK
dc.publisherAmerican Society of Hematology-
dc.relation.ispartofBlood-
dc.titleIron-overload induces apoptosis in cardiomyocytes and hepatocytes via mitochondrial/caspase-3 pathwaysen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailYang, M: yangm1091@yahoo.com.hken_HK
dc.identifier.emailChan, S: chanshing2001@hotmail.comen_HK
dc.identifier.emailCheung, YF: xfcheung@hkucc.hku.hken_HK
dc.identifier.emailHa, SY: syha@hkucc.hku.hken_HK
dc.identifier.emailChan, GCF: gcfchan@hkucc.hku.hken_HK
dc.identifier.authorityCheung, YF=rp00382en_HK
dc.identifier.authorityChan, GCF=rp00431en_HK
dc.identifier.hkuros154290en_HK

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