Catalase Mediates the Inhibitory Actions of PPARδ against Angiotensin II-Triggered Hypertrophy in H9c2 Cardiomyocytes
Hypertrophy of myocytes has been implicated in cardiac dysfunctions affecting wall stress and patterns of gene expression. However, molecular targets potentially preventing cardiac hypertrophy have not been fully elucidated. In the present study, we demonstrate that upregulation of catalase by perox...
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MDPI AG
2021-07-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/8/1223 |
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| author | Jung Seok Hwang Jinwoo Hur Won Jin Lee Jun Pil Won Hyuk Gyoon Lee Dae-Seog Lim Eunsu Kim Han Geuk Seo |
| author_facet | Jung Seok Hwang Jinwoo Hur Won Jin Lee Jun Pil Won Hyuk Gyoon Lee Dae-Seog Lim Eunsu Kim Han Geuk Seo |
| author_sort | Jung Seok Hwang |
| collection | DOAJ |
| description | Hypertrophy of myocytes has been implicated in cardiac dysfunctions affecting wall stress and patterns of gene expression. However, molecular targets potentially preventing cardiac hypertrophy have not been fully elucidated. In the present study, we demonstrate that upregulation of catalase by peroxisome proliferator-activated receptor δ (PPARδ) is involved in the anti-hypertrophic activity of PPARδ in angiotensin II (Ang II)-treated H9c2 cardiomyocytes. Activation of PPARδ by a specific ligand GW501516 significantly inhibited Ang II-induced hypertrophy and the generation of reactive oxygen species (ROS) in H9c2 cardiomyocytes. These effects of GW501516 were almost completely abolished in cells stably expressing small hairpin (sh)RNA targeting PPARδ, indicating that PPARδ mediates these effects. Significant concentration and time-dependent increases in catalase at both mRNA and protein levels were observed in GW501516-treated H9c2 cardiomyocytes. In addition, GW501516-activated PPARδ significantly enhanced catalase promoter activity and protein expression, even in the presence of Ang II. GW501516-activated PPARδ also inhibited the expression of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), which are both marker proteins for hypertrophy. The effects of GW501516 on the expression of ANP and BNP were reversed by 3-amino-1,2,4-triazole (3-AT), a catalase inhibitor. Inhibition or downregulation of catalase by 3-AT or small interfering (si)RNA, respectively, abrogated the effects of PPARδ on Ang II-induced hypertrophy and ROS generation, indicating that these effects of PPARδ are mediated through catalase induction. Furthermore, GW501516-activated PPARδ exerted catalase-dependent inhibitory effects on Ang II-induced hypertrophy by blocking p38 mitogen-activated protein kinase. Taken together, these results indicate that the anti-hypertrophic activity of PPARδ may be achieved, at least in part, by sequestering ROS through fine-tuning the expression of catalase in cardiomyocytes. |
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| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T09:03:06Z |
| publishDate | 2021-07-01 |
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| series | Antioxidants |
| spelling | doaj.art-2dfe6a4700ee46a493be9d682ff416822023-11-22T06:35:56ZengMDPI AGAntioxidants2076-39212021-07-01108122310.3390/antiox10081223Catalase Mediates the Inhibitory Actions of PPARδ against Angiotensin II-Triggered Hypertrophy in H9c2 CardiomyocytesJung Seok Hwang0Jinwoo Hur1Won Jin Lee2Jun Pil Won3Hyuk Gyoon Lee4Dae-Seog Lim5Eunsu Kim6Han Geuk Seo7College of Sang-Huh Life Sciences, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, KoreaCollege of Sang-Huh Life Sciences, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, KoreaCollege of Sang-Huh Life Sciences, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, KoreaCollege of Sang-Huh Life Sciences, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, KoreaCollege of Sang-Huh Life Sciences, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, KoreaDepartment of Biotechnology, CHA University, 355 Pangyo-ro, Bundang-gu, Seongnam 13488, KoreaCollege of Sang-Huh Life Sciences, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, KoreaCollege of Sang-Huh Life Sciences, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, KoreaHypertrophy of myocytes has been implicated in cardiac dysfunctions affecting wall stress and patterns of gene expression. However, molecular targets potentially preventing cardiac hypertrophy have not been fully elucidated. In the present study, we demonstrate that upregulation of catalase by peroxisome proliferator-activated receptor δ (PPARδ) is involved in the anti-hypertrophic activity of PPARδ in angiotensin II (Ang II)-treated H9c2 cardiomyocytes. Activation of PPARδ by a specific ligand GW501516 significantly inhibited Ang II-induced hypertrophy and the generation of reactive oxygen species (ROS) in H9c2 cardiomyocytes. These effects of GW501516 were almost completely abolished in cells stably expressing small hairpin (sh)RNA targeting PPARδ, indicating that PPARδ mediates these effects. Significant concentration and time-dependent increases in catalase at both mRNA and protein levels were observed in GW501516-treated H9c2 cardiomyocytes. In addition, GW501516-activated PPARδ significantly enhanced catalase promoter activity and protein expression, even in the presence of Ang II. GW501516-activated PPARδ also inhibited the expression of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), which are both marker proteins for hypertrophy. The effects of GW501516 on the expression of ANP and BNP were reversed by 3-amino-1,2,4-triazole (3-AT), a catalase inhibitor. Inhibition or downregulation of catalase by 3-AT or small interfering (si)RNA, respectively, abrogated the effects of PPARδ on Ang II-induced hypertrophy and ROS generation, indicating that these effects of PPARδ are mediated through catalase induction. Furthermore, GW501516-activated PPARδ exerted catalase-dependent inhibitory effects on Ang II-induced hypertrophy by blocking p38 mitogen-activated protein kinase. Taken together, these results indicate that the anti-hypertrophic activity of PPARδ may be achieved, at least in part, by sequestering ROS through fine-tuning the expression of catalase in cardiomyocytes.https://www.mdpi.com/2076-3921/10/8/1223angiotensin IIcatalasehypertrophyperoxisome proliferator-activated receptor δreactive oxygen species |
| spellingShingle | Jung Seok Hwang Jinwoo Hur Won Jin Lee Jun Pil Won Hyuk Gyoon Lee Dae-Seog Lim Eunsu Kim Han Geuk Seo Catalase Mediates the Inhibitory Actions of PPARδ against Angiotensin II-Triggered Hypertrophy in H9c2 Cardiomyocytes Antioxidants angiotensin II catalase hypertrophy peroxisome proliferator-activated receptor δ reactive oxygen species |
| title | Catalase Mediates the Inhibitory Actions of PPARδ against Angiotensin II-Triggered Hypertrophy in H9c2 Cardiomyocytes |
| title_full | Catalase Mediates the Inhibitory Actions of PPARδ against Angiotensin II-Triggered Hypertrophy in H9c2 Cardiomyocytes |
| title_fullStr | Catalase Mediates the Inhibitory Actions of PPARδ against Angiotensin II-Triggered Hypertrophy in H9c2 Cardiomyocytes |
| title_full_unstemmed | Catalase Mediates the Inhibitory Actions of PPARδ against Angiotensin II-Triggered Hypertrophy in H9c2 Cardiomyocytes |
| title_short | Catalase Mediates the Inhibitory Actions of PPARδ against Angiotensin II-Triggered Hypertrophy in H9c2 Cardiomyocytes |
| title_sort | catalase mediates the inhibitory actions of pparδ against angiotensin ii triggered hypertrophy in h9c2 cardiomyocytes |
| topic | angiotensin II catalase hypertrophy peroxisome proliferator-activated receptor δ reactive oxygen species |
| url | https://www.mdpi.com/2076-3921/10/8/1223 |
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