ALDH2 Inhibition Potentiates High Glucose Stress-Induced Injury in Cultured Cardiomyocytes
Aldehyde dehydrogenase (ALDH) gene superfamily consists of 19 isozymes. They are present in various organs and involved in metabolizing aldehydes that are biologically generated. For instance, ALDH2, a cardiac mitochondrial ALDH isozyme, is known to detoxify 4-hydroxy-2-nonenal, a reactive aldehyde...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2016/1390861 |
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| author | Guodong Pan Mandar Deshpande Rajarajan A. Thandavarayan Suresh Selvaraj Palaniyandi |
| author_facet | Guodong Pan Mandar Deshpande Rajarajan A. Thandavarayan Suresh Selvaraj Palaniyandi |
| author_sort | Guodong Pan |
| collection | DOAJ |
| description | Aldehyde dehydrogenase (ALDH) gene superfamily consists of 19 isozymes. They are present in various organs and involved in metabolizing aldehydes that are biologically generated. For instance, ALDH2, a cardiac mitochondrial ALDH isozyme, is known to detoxify 4-hydroxy-2-nonenal, a reactive aldehyde produced upon lipid peroxidation in diabetic conditions. We hypothesized that inhibition of ALDH leads to the accumulation of unmetabolized 4HNE and consequently exacerbates injury in cells subjected to high glucose stress. H9C2 cardiomyocyte cell lines were pretreated with 10 μM disulfiram (DSF), an inhibitor of ALDH2 or vehicle (DMSO) for 2 hours, and then subjected to high glucose stress {33 mM D-glucose (HG) or 33 mM D-mannitol as an osmotic control (Ctrl)} for 24 hrs. The decrease in ALDH2 activity with DSF pretreatment was higher in HG group when compared to Ctrl group. Increased 4HNE adduct formation with DSF pretreatment was higher in HG group compared to Ctrl group. Pretreatment with DSF leads to potentiated HG-induced cell death in cultured H9C2 cardiomyocytes by lowering mitochondrial membrane potential. Our results indicate that ALDH2 activity is important in preventing high glucose induced cellular dysfunction. |
| format | Article |
| id | doaj-art-1b0790a4d7bf4d44a49b82adc06aa9d5 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-1b0790a4d7bf4d44a49b82adc06aa9d52025-08-20T03:54:24ZengWileyJournal of Diabetes Research2314-67452314-67532016-01-01201610.1155/2016/13908611390861ALDH2 Inhibition Potentiates High Glucose Stress-Induced Injury in Cultured CardiomyocytesGuodong Pan0Mandar Deshpande1Rajarajan A. Thandavarayan2Suresh Selvaraj Palaniyandi3Division of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Health System, Detroit, MI 48202, USADivision of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Health System, Detroit, MI 48202, USADepartment of Cardiovascular Sciences, Center for Cardiovascular Regeneration, Houston Methodist Research Institute, Houston, TX, USADivision of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Health System, Detroit, MI 48202, USAAldehyde dehydrogenase (ALDH) gene superfamily consists of 19 isozymes. They are present in various organs and involved in metabolizing aldehydes that are biologically generated. For instance, ALDH2, a cardiac mitochondrial ALDH isozyme, is known to detoxify 4-hydroxy-2-nonenal, a reactive aldehyde produced upon lipid peroxidation in diabetic conditions. We hypothesized that inhibition of ALDH leads to the accumulation of unmetabolized 4HNE and consequently exacerbates injury in cells subjected to high glucose stress. H9C2 cardiomyocyte cell lines were pretreated with 10 μM disulfiram (DSF), an inhibitor of ALDH2 or vehicle (DMSO) for 2 hours, and then subjected to high glucose stress {33 mM D-glucose (HG) or 33 mM D-mannitol as an osmotic control (Ctrl)} for 24 hrs. The decrease in ALDH2 activity with DSF pretreatment was higher in HG group when compared to Ctrl group. Increased 4HNE adduct formation with DSF pretreatment was higher in HG group compared to Ctrl group. Pretreatment with DSF leads to potentiated HG-induced cell death in cultured H9C2 cardiomyocytes by lowering mitochondrial membrane potential. Our results indicate that ALDH2 activity is important in preventing high glucose induced cellular dysfunction.http://dx.doi.org/10.1155/2016/1390861 |
| spellingShingle | Guodong Pan Mandar Deshpande Rajarajan A. Thandavarayan Suresh Selvaraj Palaniyandi ALDH2 Inhibition Potentiates High Glucose Stress-Induced Injury in Cultured Cardiomyocytes Journal of Diabetes Research |
| title | ALDH2 Inhibition Potentiates High Glucose Stress-Induced Injury in Cultured Cardiomyocytes |
| title_full | ALDH2 Inhibition Potentiates High Glucose Stress-Induced Injury in Cultured Cardiomyocytes |
| title_fullStr | ALDH2 Inhibition Potentiates High Glucose Stress-Induced Injury in Cultured Cardiomyocytes |
| title_full_unstemmed | ALDH2 Inhibition Potentiates High Glucose Stress-Induced Injury in Cultured Cardiomyocytes |
| title_short | ALDH2 Inhibition Potentiates High Glucose Stress-Induced Injury in Cultured Cardiomyocytes |
| title_sort | aldh2 inhibition potentiates high glucose stress induced injury in cultured cardiomyocytes |
| url | http://dx.doi.org/10.1155/2016/1390861 |
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