RGD Reference Report - Homocysteine induces cardiac hypertrophy by up-regulating ATP7a expression. - Rat Genome Database

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Homocysteine induces cardiac hypertrophy by up-regulating ATP7a expression.

Authors: Cao, Z  Zhang, Y  Sun, T  Zhang, S  Yu, W  Zhu, J 
Citation: Cao Z, etal., Int J Clin Exp Pathol. 2015 Oct 1;8(10):12829-36. eCollection 2015.
RGD ID: 11341663
Pubmed: (View Article at PubMed) PMID:26722473

AIMS: The aim of the study is to investigate the molecular mechanism by which homocysteine (Hcy) induces cardiac hypertrophy. METHODS: Primary cardiomyocytes were obtained from baby Sprague-Dawley rats within 3 days after birth. Flow cytometry was used to measure cell sizes. Quantitative real-time polymerase chain reaction was performed to measure the expression of beta-myosin heavy chain and atrial natriuretic peptide genes. Western blotting assay was employed to determine ATP7a protein expression. Cytochrome C oxidase (COX) activity test was used to evaluate the activity of COX. Atomic absorption spectroscopy was performed to determine copper content. siRNAs were used to target-silence the expression of ATP7a. RESULTS: Hcy induced cardiac hypertrophy and increased the expression of cardiac hypertrophy-related genes. ATP7a was a key factor in cardiac hypertrophy induced by Hcy. Reduced ATP7a expression inhibited cardiac hypertrophy induced by Hcy. Elevated ATP7a expression induced by Hcy inhibited COX activity. Enhanced ATP7a expression inhibited COX activity by lowering intracellular copper content. CONCLUSIONS: Hcy elevates ATP7a protein expression, reduces copper content, and lowers COX activity, finally leading to cardiac hypertrophy.

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Atp7a  (ATPase copper transporting alpha)

Additional Information