The involvement of N-G,N-G-dimethyarginine dimethylhydrolase 1 in the proliferative effect of Astragali radix on cardiac cells.
OBJECTIVE
Astragali radix (AR) is a widely used traditional medicine in oriental countries for treating various diseases including cardiovascular disease (CVD). We investigated the effects of AR extracts on rat cardiomyocytes and H9C2 cardiac cells as well as identified many target genes that mediate the effect of AR.


METHODS
The effect of AR extracts on cell proliferation was assessed and cDNA microarray technique was used to analyse the differential gene expressions upon AR treatment in cardiac cells. One of the selected target genes was over-expressed to elucidate its role in cell proliferation.


RESULTS
AR was shown to promote the proliferation of neonatal rat cardiomyocytes and H9C2 cells. Results of cDNA microarray hybridization showed that N-G,N-G-dimethylarginine dimethylaminohydrolase 1 (DDAH1) gene was up-regulated in AR-treated H9C2 cells and the results were further confirmed by reverse transcription polymerase chain reaction. Over-expression of DDAH1 gene in H9C2 cells significantly enhances the cell proliferation. Moreover, a drastic drop of DDAH1 expression in rat ventricular myocardium was observed from day 3 to day 5 after birth, which is the critical transition of cardiomyocytes from hyperplastic to hypertrophic growth.


CONCLUSIONS
AR promotes cardiac cell proliferation and up-regulates the DDAH1, an enzyme that metabolized the endogenous nitric oxide (NO) synthase inhibitor. The effect of AR on the metabolism of NO deserves future investigation.
School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
Cindy S L
CS
Law
Pui-Yin
PY
Leung
Patrick K S
PK
Ng
Cecy Y C
CY
Kou
Karen K W
KK
Au
Junwei
J
Zhou
Stephen K W
SK
Tsui
D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D027883:Astragalus Plant / Q000737:chemistry; D001483:Base Sequence; D049109:Cell Proliferation / Q000187:drug effects*; D017931:DNA Primers; D015870:Gene Expression / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D010936:Plant Extracts; D000581:Amidohydrolases; C059999:dimethylargininase