Abstract |
Hypertension causes cardiac hypertrophy and leads to heart failure. Apoptotic cells are common in hypertensive hearts. Ca2+ / calmodulin-dependent protein kinase II ( CaMKII) is associated with apoptosis. We recently demonstrated that gallic acid reduces nitric oxide synthase inhibition-induced hypertension. Gallic acid is a trihydroxybenzoic acid and has been shown to have beneficial effects, such as anti- cancer, anti-calcification and anti-oxidant activity. The purpose of this study was to determine whether gallic acid regulates cardiac hypertrophy and apoptosis in essential hypertension. Gallic acid significantly lowered systolic and diastolic blood pressure in spontaneously hypertensive rats (SHRs). Wheat germ agglutinin (WGA) and H&E staining revealed that gallic acid reduced cardiac enlargement in SHRs. Gallic acid treatment decreased cardiac hypertrophy marker genes, including atrial natriuretic peptide ( ANP) and brain natriuretic peptide (BNP), in SHRs. The four isoforms, α, β, δ and γ, of CaMKII were increased in SHRs and were significantly reduced by gallic acid administration. Gallic acid reduced cleaved caspase-3 protein as well as bax, p53 and p300 mRNA levels in SHRs. CaMKII δ overexpression induced bax and p53 expression, which was attenuated by gallic acid treatment in H9c2 cells. Gallic acid treatment reduced DNA fragmentation and the TUNEL positive cells induced by angiotensin II. Taken together, gallic acid could be a novel therapeutic for the treatment of hypertension through suppression of CaMKII δ-induced apoptosis.
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Authors | Li Jin, Zhe Hao Piao, Chun Ping Liu, Simei Sun, Bin Liu, Gwi Ran Kim, Sin Young Choi, Yuhee Ryu, Hae Jin Kee, Myung Ho Jeong |
Journal | Journal of cellular and molecular medicine
(J Cell Mol Med)
Vol. 22
Issue 3
Pg. 1517-1526
(03 2018)
ISSN: 1582-4934 [Electronic] England |
PMID | 29266709
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. |
Chemical References |
- Antihypertensive Agents
- Bax protein, rat
- Cardiotonic Agents
- Isoenzymes
- Tumor Suppressor Protein p53
- bcl-2-Associated X Protein
- Angiotensin II
- Natriuretic Peptide, Brain
- Gallic Acid
- Atrial Natriuretic Factor
- Nitric Oxide Synthase
- p300-CBP Transcription Factors
- p300-CBP-associated factor
- Calcium-Calmodulin-Dependent Protein Kinase Type 2
- Casp3 protein, rat
- Caspase 3
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Topics |
- Angiotensin II
(pharmacology)
- Animals
- Antihypertensive Agents
(pharmacology)
- Apoptosis
(drug effects, genetics)
- Atrial Natriuretic Factor
(genetics, metabolism)
- Blood Pressure
(drug effects)
- Calcium-Calmodulin-Dependent Protein Kinase Type 2
(antagonists & inhibitors, genetics, metabolism)
- Cardiotonic Agents
(pharmacology)
- Caspase 3
(genetics, metabolism)
- Cell Line
- Gallic Acid
(pharmacology)
- Gene Expression Regulation
- Hypertension
(drug therapy, enzymology, genetics, pathology)
- Hypertrophy, Left Ventricular
(drug therapy, enzymology, genetics, pathology)
- Isoenzymes
(antagonists & inhibitors, genetics, metabolism)
- Male
- Myocytes, Cardiac
(drug effects, enzymology, pathology)
- Natriuretic Peptide, Brain
(genetics, metabolism)
- Nitric Oxide Synthase
(genetics, metabolism)
- Rats
- Rats, Inbred SHR
- Rats, Inbred WKY
- Signal Transduction
- Tumor Suppressor Protein p53
(genetics, metabolism)
- bcl-2-Associated X Protein
(genetics, metabolism)
- p300-CBP Transcription Factors
(genetics, metabolism)
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