EPIGALLOCATECHIN-3-GALLATE ATTENUATES CARDIAC HYPERTROPHY IN HYPERTENSIVE RATS IN PART BY MODULATION OF MITOGEN-ACTIVATED PROTEIN KINASE SIGNALS

Autor: Yu-gang Dong, Dan Liu, Dan-Dan Chen, Jian-gui He
Rok vydání: 2009
Předmět:
Male
Physiology
Respiratory chain
p38 Mitogen-Activated Protein Kinases
Antioxidants
Catechin
Mitochondria
Heart
Muscle hypertrophy
Rats
Sprague-Dawley
chemistry.chemical_compound
Atrial natriuretic peptide
Ventricular hypertrophy
Malondialdehyde
Natriuretic Peptide
Brain
Phosphorylation
Mitogen-Activated Protein Kinase 1
chemistry.chemical_classification
Glutathione peroxidase
NF-kappa B
food and beverages
Catalase
Brain natriuretic peptide
Matrix Metalloproteinase 9
Hypertension
Matrix Metalloproteinase 2
Hypertrophy
Left Ventricular
Mitogen-Activated Protein Kinases
Atrial Natriuretic Factor
medicine.medical_specialty
MAP Kinase Signaling System
Biology
DNA
Mitochondrial
Physiology (medical)
Internal medicine
medicine
Animals
Mitogen-Activated Protein Kinase 8
Pharmacology
Glutathione Peroxidase
Reactive oxygen species
Myosin Heavy Chains
Superoxide Dismutase
Myocardium
Hemodynamics
medicine.disease
Rats
Enzyme Activation
Transcription Factor AP-1
Disease Models
Animal
Endocrinology
Electron Transport Chain Complex Proteins
chemistry
Reactive Oxygen Species
Zdroj: Clinical and Experimental Pharmacology and Physiology. 36:925-932
ISSN: 1440-1681
0305-1870
Popis: SUMMARY 1It has been demonstrated that epigallocatechin-3-gallate (EGCG) inhibits cardiac hypertrophy through its antihypertensive and anti-oxidant effects. However, the underlying molecular mechanism is not clear. 2In the present study, we tested the hypothesis that EGCG attenuates transaortic abdominal aortic constriction (TAC)-induced ventricular hypertrophy by regulating mitogen-activated protein kinase (MAPK) signal pathways in hypertensive rats. Four groups of rats were used: (i) a sham-operated control group; (ii) an EGCG-treated (50 mg/kg per day, i.p., for 21 days) sham-operated group; (iii) a TAC group; and (iv) an EGCG-treated TAC group. Histological analysis of whole hearts and biochemical analyses of left ventricular (LV) tissue were used to investigate the effects of EGCG. 3The results showed that the LV myocyte diameter and the expression of atrial natriuretic peptide, brain natriuretic peptide and β-myocardial heavy chain were significantly decreased in the EGCG-treated (50 mg/kg per day, i.p.) TAC group. Levels of reactive oxygen species and malondialdehyde in the lV were significantly reduced by EGCG in the TAC group. Total superoxide dismutase, catalase and glutathione peroxidase activities were decreased in the TAC group, and this decrease was significantly restored by EGCG treatment. Phosphorylation of extracellular signal-regulated kinase 2, p38 and c-Jun N-terminal kinase 1 was significantly reversed in the LV of EGCG-treated TAC rats (40%, 53% and 52%vs TAC, respectively), accompanied by significant inhibition of nuclear factor-κB and activator protein-1. Transaortic abdominal aortic constriction significantly upregulated LV expression of matrix metalloproteinase-9 from 32 ± 6 to 100 ± 12% and this increase was inhibited by EGCG treatment (from 100 ± 12 to 50 ± 15%). In addition, TAC decreased mitochondrial DNA copy number and the activity of respiratory chain complexes I (from 100 ± 7 to 68 ± 5%), III (from 100 ± 4 to 2 ± 5%) and IV (from 766 ± 2 to 100 ± 5%); this decrease was reversed by EGCG treatment to levels seen in sham-operated rats. 4In conclusion, EGCG attenuates TAC-induced ventricular hypertrophy in hypertensive rats in part by suppression of anti-oxidant enzymes and regulation of MAPK signals.
Databáze: OpenAIRE
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