Differential changes in cyclic adenosine 3′-5′ monophosphate (cAMP) effectors and major Ca2+ handling proteins during diabetic cardiomyopathy
Diabetic cardiomyopathy (DCM) is associated with differential and time-specific regulation of β-adrenergic receptors and cardiac cyclic nucleotide phosphodiesterases with consequences for total cyclic adenosine 3′-5′ monophosphate (cAMP) levels. We aimed to investigate whether these changes are asso...
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2023
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| Online Access: | http://hdl.handle.net/10725/14634 https://doi.org/10.1111/jcmm.17733 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.17733 |
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| _version_ | 1864513469661839360 |
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| author | Chaoul, Victoria |
| author2 | Hanna, Rita Hachem, Pia El Hayek, Magali Samia Nour-Eldine, Wared Abou-Khalil, Pamela Abi-Ramia, Elias Vandecasteele, Grégoire Abi-Gerges, Aniella |
| author2_role | author author author author author author author author |
| author_facet | Chaoul, Victoria Hanna, Rita Hachem, Pia El Hayek, Magali Samia Nour-Eldine, Wared Abou-Khalil, Pamela Abi-Ramia, Elias Vandecasteele, Grégoire Abi-Gerges, Aniella |
| author_role | author |
| dc.creator.none.fl_str_mv | Chaoul, Victoria Hanna, Rita Hachem, Pia El Hayek, Magali Samia Nour-Eldine, Wared Abou-Khalil, Pamela Abi-Ramia, Elias Vandecasteele, Grégoire Abi-Gerges, Aniella |
| dc.date.none.fl_str_mv | 2023-04-04T13:17:00Z 2023-04-04T13:17:00Z 2023 2023-03-27 |
| dc.identifier.none.fl_str_mv | 1582-1838 http://hdl.handle.net/10725/14634 https://doi.org/10.1111/jcmm.17733 Chaoul, V., Hanna, R., Hachem, P., El Hayek, M. S., Nour‐Eldine, W., Abou‐Khalil, P., ... & Abi‐Gerges, A. (2023). Differential changes in cyclic adenosine 3′‐5′ monophosphate (cAMP) effectors and major Ca2+ handling proteins during diabetic cardiomyopathy. Journal of Cellular and Molecular Medicine, 27(9), 1277-1289. http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.17733 |
| dc.language.none.fl_str_mv | en |
| dc.relation.none.fl_str_mv | Journal of Cellular and Molecular Medicine |
| dc.rights.*.fl_str_mv | info:eu-repo/semantics/openAccess |
| dc.title.none.fl_str_mv | Differential changes in cyclic adenosine 3′-5′ monophosphate (cAMP) effectors and major Ca2+ handling proteins during diabetic cardiomyopathy |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | Diabetic cardiomyopathy (DCM) is associated with differential and time-specific regulation of β-adrenergic receptors and cardiac cyclic nucleotide phosphodiesterases with consequences for total cyclic adenosine 3′-5′ monophosphate (cAMP) levels. We aimed to investigate whether these changes are associated with downstream impairments in cAMP and Ca2+ signalling in a type 1 diabetes (T1D)-induced DCM model. T1D was induced in adult male rats by streptozotocin (65 mg/kg) injection. DCM was assessed by cardiac structural and molecular remodelling. We delineated sequential changes affecting the exchange protein (Epac1/2), cAMP-dependent protein kinase A (PKA) and Ca2+/Calmodulin-dependent kinase II (CaMKII) at 4, 8 and 12 weeks following diabetes, by real-time quantitative PCR and western blot. Expression of Ca2+ ATPase pump (SERCA2a), phospholamban (PLB) and Troponin I (TnI) was also examined. Early upregulation of Epac1 transcripts was noted in diabetic hearts at Week 4, followed by increases in Epac2 mRNA, but not protein levels, at Week 12. Expression of PKA subunits (RI, RIIα and Cα) remained unchanged regardless of the disease stage, whereas CaMKII increased at Week 12 in DCM. Moreover, PLB transcripts were upregulated in diabetic hearts, whereas SERCA2a and TnI gene expression was unchanged irrespective of the disease evolution. PLB phosphorylation at threonine-17 was increased in DCM, whereas phosphorylation of both PLB at serine-16 and TnI at serine-23/24 was unchanged. We show for the first time differential and time-specific regulations in cardiac cAMP effectors and Ca2+ handling proteins, data that may prove useful in proposing new therapeutic approaches in T1D-induced DCM. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | LAURepo_65b235f442901bd2da4bcdb112eb26c8 |
| identifier_str_mv | 1582-1838 Chaoul, V., Hanna, R., Hachem, P., El Hayek, M. S., Nour‐Eldine, W., Abou‐Khalil, P., ... & Abi‐Gerges, A. (2023). Differential changes in cyclic adenosine 3′‐5′ monophosphate (cAMP) effectors and major Ca2+ handling proteins during diabetic cardiomyopathy. Journal of Cellular and Molecular Medicine, 27(9), 1277-1289. |
| language_invalid_str_mv | en |
| network_acronym_str | LAURepo |
| network_name_str | Lebanese American University repository |
| oai_identifier_str | oai:laur.lau.edu.lb:10725/14634 |
| publishDate | 2023 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| spelling | Differential changes in cyclic adenosine 3′-5′ monophosphate (cAMP) effectors and major Ca2+ handling proteins during diabetic cardiomyopathyChaoul, VictoriaHanna, RitaHachem, PiaEl Hayek, Magali SamiaNour-Eldine, WaredAbou-Khalil, PamelaAbi-Ramia, EliasVandecasteele, GrégoireAbi-Gerges, AniellaDiabetic cardiomyopathy (DCM) is associated with differential and time-specific regulation of β-adrenergic receptors and cardiac cyclic nucleotide phosphodiesterases with consequences for total cyclic adenosine 3′-5′ monophosphate (cAMP) levels. We aimed to investigate whether these changes are associated with downstream impairments in cAMP and Ca2+ signalling in a type 1 diabetes (T1D)-induced DCM model. T1D was induced in adult male rats by streptozotocin (65 mg/kg) injection. DCM was assessed by cardiac structural and molecular remodelling. We delineated sequential changes affecting the exchange protein (Epac1/2), cAMP-dependent protein kinase A (PKA) and Ca2+/Calmodulin-dependent kinase II (CaMKII) at 4, 8 and 12 weeks following diabetes, by real-time quantitative PCR and western blot. Expression of Ca2+ ATPase pump (SERCA2a), phospholamban (PLB) and Troponin I (TnI) was also examined. Early upregulation of Epac1 transcripts was noted in diabetic hearts at Week 4, followed by increases in Epac2 mRNA, but not protein levels, at Week 12. Expression of PKA subunits (RI, RIIα and Cα) remained unchanged regardless of the disease stage, whereas CaMKII increased at Week 12 in DCM. Moreover, PLB transcripts were upregulated in diabetic hearts, whereas SERCA2a and TnI gene expression was unchanged irrespective of the disease evolution. PLB phosphorylation at threonine-17 was increased in DCM, whereas phosphorylation of both PLB at serine-16 and TnI at serine-23/24 was unchanged. We show for the first time differential and time-specific regulations in cardiac cAMP effectors and Ca2+ handling proteins, data that may prove useful in proposing new therapeutic approaches in T1D-induced DCM.Published2023-04-04T13:17:00Z2023-04-04T13:17:00Z20232023-03-27Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1582-1838http://hdl.handle.net/10725/14634https://doi.org/10.1111/jcmm.17733Chaoul, V., Hanna, R., Hachem, P., El Hayek, M. S., Nour‐Eldine, W., Abou‐Khalil, P., ... & Abi‐Gerges, A. (2023). Differential changes in cyclic adenosine 3′‐5′ monophosphate (cAMP) effectors and major Ca2+ handling proteins during diabetic cardiomyopathy. Journal of Cellular and Molecular Medicine, 27(9), 1277-1289.http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.phphttps://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.17733enJournal of Cellular and Molecular Medicineinfo:eu-repo/semantics/openAccessoai:laur.lau.edu.lb:10725/146342024-07-12T06:54:14Z |
| spellingShingle | Differential changes in cyclic adenosine 3′-5′ monophosphate (cAMP) effectors and major Ca2+ handling proteins during diabetic cardiomyopathy Chaoul, Victoria |
| status_str | publishedVersion |
| title | Differential changes in cyclic adenosine 3′-5′ monophosphate (cAMP) effectors and major Ca2+ handling proteins during diabetic cardiomyopathy |
| title_full | Differential changes in cyclic adenosine 3′-5′ monophosphate (cAMP) effectors and major Ca2+ handling proteins during diabetic cardiomyopathy |
| title_fullStr | Differential changes in cyclic adenosine 3′-5′ monophosphate (cAMP) effectors and major Ca2+ handling proteins during diabetic cardiomyopathy |
| title_full_unstemmed | Differential changes in cyclic adenosine 3′-5′ monophosphate (cAMP) effectors and major Ca2+ handling proteins during diabetic cardiomyopathy |
| title_short | Differential changes in cyclic adenosine 3′-5′ monophosphate (cAMP) effectors and major Ca2+ handling proteins during diabetic cardiomyopathy |
| title_sort | Differential changes in cyclic adenosine 3′-5′ monophosphate (cAMP) effectors and major Ca2+ handling proteins during diabetic cardiomyopathy |
| url | http://hdl.handle.net/10725/14634 https://doi.org/10.1111/jcmm.17733 http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.17733 |