Esculetin reverses histone H2A/H2B ubiquitination, H3 dimethylation, acetylation and phosphorylation in preventing type 2 diabetic cardiomyopathy
Post translational histone modifications (PTHMs) play a pivotal role in pathogenesis of diabetic complications. Esculetin is reported to prevent glomerulosclerosis by reversing PTHMs in diabetic rats, but until now its cardioprotective role is unexplored. Hence, the present study aimed to investigat...
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Elsevier
2015-08-01
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| Series: | Journal of Functional Foods |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1756464615002558 |
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| author | Almesh Kadakol Vajir Malek Santosh Kumar Goru Anuradha Pandey Anil Bhanudas Gaikwad |
| author_facet | Almesh Kadakol Vajir Malek Santosh Kumar Goru Anuradha Pandey Anil Bhanudas Gaikwad |
| author_sort | Almesh Kadakol |
| collection | DOAJ |
| description | Post translational histone modifications (PTHMs) play a pivotal role in pathogenesis of diabetic complications. Esculetin is reported to prevent glomerulosclerosis by reversing PTHMs in diabetic rats, but until now its cardioprotective role is unexplored. Hence, the present study aimed to investigate the effect of esculetin on diabetic cardiomyopathy (DCM) and its associated PTHMs. Insulin resistance (IR) and type 2 diabetic rats' heart had augmented permissive PTHMs which contributed to DCM. Besides this, for the first time we have demonstrated increased histone H2AK119Ub and H2BK120Ub levels in DCM. Esculetin treatment reduced metabolic alterations, hypertension, cardiomyocytes hypertrophy, and fibrosis in the diabetic heart. In addition, esculetin attenuated alteration in the renin–angiotensin system, oxidative stress (Keap1) and cell proliferation (Ki67); thus preventing DCM. Remarkably, esculetin treatment restored normal level of permissive PTHMs and H2A/H2B ubiquitination in IR and diabetic heart which might be the basic mechanism behind its cardioprotective role. |
| first_indexed | 2024-12-21T13:53:13Z |
| format | Article |
| id | doaj.art-10777474206d46f18ffd7917a82e7351 |
| institution | Directory Open Access Journal |
| issn | 1756-4646 |
| language | English |
| last_indexed | 2024-12-21T13:53:13Z |
| publishDate | 2015-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Functional Foods |
| spelling | doaj.art-10777474206d46f18ffd7917a82e73512022-12-21T19:01:38ZengElsevierJournal of Functional Foods1756-46462015-08-0117127136Esculetin reverses histone H2A/H2B ubiquitination, H3 dimethylation, acetylation and phosphorylation in preventing type 2 diabetic cardiomyopathyAlmesh Kadakol0Vajir Malek1Santosh Kumar Goru2Anuradha Pandey3Anil Bhanudas Gaikwad4Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan 333031, IndiaLaboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan 333031, IndiaLaboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan 333031, IndiaLaboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan 333031, IndiaCorresponding author. Department of Pharmacy, Birla Institute of Technology and Science, Pilani Campus, Pilani, 333031 Rajasthan, India. Tel.: +91 1596 515717; fax: +91 1596 244183.; Laboratory of Molecular Pharmacology, Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Rajasthan 333031, IndiaPost translational histone modifications (PTHMs) play a pivotal role in pathogenesis of diabetic complications. Esculetin is reported to prevent glomerulosclerosis by reversing PTHMs in diabetic rats, but until now its cardioprotective role is unexplored. Hence, the present study aimed to investigate the effect of esculetin on diabetic cardiomyopathy (DCM) and its associated PTHMs. Insulin resistance (IR) and type 2 diabetic rats' heart had augmented permissive PTHMs which contributed to DCM. Besides this, for the first time we have demonstrated increased histone H2AK119Ub and H2BK120Ub levels in DCM. Esculetin treatment reduced metabolic alterations, hypertension, cardiomyocytes hypertrophy, and fibrosis in the diabetic heart. In addition, esculetin attenuated alteration in the renin–angiotensin system, oxidative stress (Keap1) and cell proliferation (Ki67); thus preventing DCM. Remarkably, esculetin treatment restored normal level of permissive PTHMs and H2A/H2B ubiquitination in IR and diabetic heart which might be the basic mechanism behind its cardioprotective role.http://www.sciencedirect.com/science/article/pii/S1756464615002558EpigeneticsDiabetic cardiomyopathyEsculetinHistone H3 and H2 modifications |
| spellingShingle | Almesh Kadakol Vajir Malek Santosh Kumar Goru Anuradha Pandey Anil Bhanudas Gaikwad Esculetin reverses histone H2A/H2B ubiquitination, H3 dimethylation, acetylation and phosphorylation in preventing type 2 diabetic cardiomyopathy Journal of Functional Foods Epigenetics Diabetic cardiomyopathy Esculetin Histone H3 and H2 modifications |
| title | Esculetin reverses histone H2A/H2B ubiquitination, H3 dimethylation, acetylation and phosphorylation in preventing type 2 diabetic cardiomyopathy |
| title_full | Esculetin reverses histone H2A/H2B ubiquitination, H3 dimethylation, acetylation and phosphorylation in preventing type 2 diabetic cardiomyopathy |
| title_fullStr | Esculetin reverses histone H2A/H2B ubiquitination, H3 dimethylation, acetylation and phosphorylation in preventing type 2 diabetic cardiomyopathy |
| title_full_unstemmed | Esculetin reverses histone H2A/H2B ubiquitination, H3 dimethylation, acetylation and phosphorylation in preventing type 2 diabetic cardiomyopathy |
| title_short | Esculetin reverses histone H2A/H2B ubiquitination, H3 dimethylation, acetylation and phosphorylation in preventing type 2 diabetic cardiomyopathy |
| title_sort | esculetin reverses histone h2a h2b ubiquitination h3 dimethylation acetylation and phosphorylation in preventing type 2 diabetic cardiomyopathy |
| topic | Epigenetics Diabetic cardiomyopathy Esculetin Histone H3 and H2 modifications |
| url | http://www.sciencedirect.com/science/article/pii/S1756464615002558 |
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