Thiamine Ameliorates Diabetes-Induced Inhibition of Pyruvate Dehydrogenase (PDH) in Rat Heart Mitochondria: Investigating the Discrepancy Between PDH Activity and PDH E1α Phosphorylation in Cardiac Fibroblasts Exposed to High Glucose
The activity of pyruvate dehydrogenase (PDH) is reduced in diabetic patients. Phosphorylation of the PDH E1α subunit by PDH kinase contributes to the suppression of PDH activity. PDH requires thiamine as a coenzyme. We investigated the exact mechanism of diabetes-induced PDH inhibition, and the effe...
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| Format: | Article |
| Language: | English |
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Elsevier
2010-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319309016 |
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| author | Yuka Kohda Masashi Umeki Tatsuji Kono Fumio Terasaki Hitoshi Matsumura Takao Tanaka |
| author_facet | Yuka Kohda Masashi Umeki Tatsuji Kono Fumio Terasaki Hitoshi Matsumura Takao Tanaka |
| author_sort | Yuka Kohda |
| collection | DOAJ |
| description | The activity of pyruvate dehydrogenase (PDH) is reduced in diabetic patients. Phosphorylation of the PDH E1α subunit by PDH kinase contributes to the suppression of PDH activity. PDH requires thiamine as a coenzyme. We investigated the exact mechanism of diabetes-induced PDH inhibition, and the effect of thiamine in both in vivo and in vitro experiments. Treatment of rats with thiamine significantly, although partially, recovered streptozotocin (STZ)-induced reductions in mitochondrial PDH activity. Nevertheless, we found that PDH E1α phosphorylation in the thiamine-treated STZ group was perfectly diminished to the same level as that in the control group. STZ treatment significantly caused enhancements of the expression of O-glycosylated protein in the rat hearts, which was decreased by thiamine repletion. Next, the rat cardiac fibroblasts (RCFs) were cultured in the presence of high glucose levels. Thiamine dramatically recovered high glucose–induced PDH inhibition. High glucose loads did not alter the phosphorylated PDH E1α. PDH inhibition in RCFs was not accompanied by an increase in the PDH E1α phosphorylation. The O-glycosylated protein was markedly increased in RCFs exposed to high glucose, which was inhibited by thiamine. These results suggest that thiamine ameliorates diabetes-induced PDH inhibition by suppressing the increased expression of the O-glycosylated protein. The O-glycosylation of PDH E1α may be involved in the regulation of the PDH activity. Keywords:: thiamine, pyruvate dehydrogenase (PDH) activity, phosphorylated PDH E1 α, O-glycosylated protein, diabetic rat heart |
| first_indexed | 2024-12-23T11:14:39Z |
| format | Article |
| id | doaj.art-c8e85ae83d1443c9a31a672abd3fd568 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-23T11:14:39Z |
| publishDate | 2010-01-01 |
| publisher | Elsevier |
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| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-c8e85ae83d1443c9a31a672abd3fd5682022-12-21T17:49:15ZengElsevierJournal of Pharmacological Sciences1347-86132010-01-011134343352Thiamine Ameliorates Diabetes-Induced Inhibition of Pyruvate Dehydrogenase (PDH) in Rat Heart Mitochondria: Investigating the Discrepancy Between PDH Activity and PDH E1α Phosphorylation in Cardiac Fibroblasts Exposed to High GlucoseYuka Kohda0Masashi Umeki1Tatsuji Kono2Fumio Terasaki3Hitoshi Matsumura4Takao Tanaka5Laboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan; Corresponding author. ykohda@gly.oups.ac.jpLaboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, JapanThird Division, Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, JapanThird Division, Department of Internal Medicine, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, JapanLaboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, JapanLaboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, JapanThe activity of pyruvate dehydrogenase (PDH) is reduced in diabetic patients. Phosphorylation of the PDH E1α subunit by PDH kinase contributes to the suppression of PDH activity. PDH requires thiamine as a coenzyme. We investigated the exact mechanism of diabetes-induced PDH inhibition, and the effect of thiamine in both in vivo and in vitro experiments. Treatment of rats with thiamine significantly, although partially, recovered streptozotocin (STZ)-induced reductions in mitochondrial PDH activity. Nevertheless, we found that PDH E1α phosphorylation in the thiamine-treated STZ group was perfectly diminished to the same level as that in the control group. STZ treatment significantly caused enhancements of the expression of O-glycosylated protein in the rat hearts, which was decreased by thiamine repletion. Next, the rat cardiac fibroblasts (RCFs) were cultured in the presence of high glucose levels. Thiamine dramatically recovered high glucose–induced PDH inhibition. High glucose loads did not alter the phosphorylated PDH E1α. PDH inhibition in RCFs was not accompanied by an increase in the PDH E1α phosphorylation. The O-glycosylated protein was markedly increased in RCFs exposed to high glucose, which was inhibited by thiamine. These results suggest that thiamine ameliorates diabetes-induced PDH inhibition by suppressing the increased expression of the O-glycosylated protein. The O-glycosylation of PDH E1α may be involved in the regulation of the PDH activity. Keywords:: thiamine, pyruvate dehydrogenase (PDH) activity, phosphorylated PDH E1 α, O-glycosylated protein, diabetic rat hearthttp://www.sciencedirect.com/science/article/pii/S1347861319309016 |
| spellingShingle | Yuka Kohda Masashi Umeki Tatsuji Kono Fumio Terasaki Hitoshi Matsumura Takao Tanaka Thiamine Ameliorates Diabetes-Induced Inhibition of Pyruvate Dehydrogenase (PDH) in Rat Heart Mitochondria: Investigating the Discrepancy Between PDH Activity and PDH E1α Phosphorylation in Cardiac Fibroblasts Exposed to High Glucose Journal of Pharmacological Sciences |
| title | Thiamine Ameliorates Diabetes-Induced Inhibition of Pyruvate Dehydrogenase (PDH) in Rat Heart Mitochondria: Investigating the Discrepancy Between PDH Activity and PDH E1α Phosphorylation in Cardiac Fibroblasts Exposed to High Glucose |
| title_full | Thiamine Ameliorates Diabetes-Induced Inhibition of Pyruvate Dehydrogenase (PDH) in Rat Heart Mitochondria: Investigating the Discrepancy Between PDH Activity and PDH E1α Phosphorylation in Cardiac Fibroblasts Exposed to High Glucose |
| title_fullStr | Thiamine Ameliorates Diabetes-Induced Inhibition of Pyruvate Dehydrogenase (PDH) in Rat Heart Mitochondria: Investigating the Discrepancy Between PDH Activity and PDH E1α Phosphorylation in Cardiac Fibroblasts Exposed to High Glucose |
| title_full_unstemmed | Thiamine Ameliorates Diabetes-Induced Inhibition of Pyruvate Dehydrogenase (PDH) in Rat Heart Mitochondria: Investigating the Discrepancy Between PDH Activity and PDH E1α Phosphorylation in Cardiac Fibroblasts Exposed to High Glucose |
| title_short | Thiamine Ameliorates Diabetes-Induced Inhibition of Pyruvate Dehydrogenase (PDH) in Rat Heart Mitochondria: Investigating the Discrepancy Between PDH Activity and PDH E1α Phosphorylation in Cardiac Fibroblasts Exposed to High Glucose |
| title_sort | thiamine ameliorates diabetes induced inhibition of pyruvate dehydrogenase pdh in rat heart mitochondria investigating the discrepancy between pdh activity and pdh e1α phosphorylation in cardiac fibroblasts exposed to high glucose |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319309016 |
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