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Lovastatin changes activities of lactate dehydrogenase A and B genes in rat myocardial cells
Wei-Zao Guo1, Hong Ji, Zhi-Hong Yan
1Department of Geriatrics, Aerospace Central Hospital, Beijing 100049, China. gwz501@hotmail.com
Insights
Lovastatin differentially impacts lactate dehydrogenase A (LDHA) and B (LDHB) gene expression in heart cells. This study reveals distinct effects on LDHA and LDHB at both mRNA and protein levels, suggesting novel pharmacological actions.
Area of Science:
- Biochemistry
- Molecular Biology
- Cardiology
Background:
- Lactate dehydrogenase (LDH) is vital for energy metabolism in organs like the heart.
- Lovastatin, a common drug for coronary heart disease, has significant metabolic effects.
- Understanding lovastatin's influence on LDH is crucial for its therapeutic application.
Purpose of the Study:
- To investigate the impact of lovastatin on the activities of lactate dehydrogenase A (LDHA) and lactate dehydrogenase B (LDHB) genes.
- To analyze changes at both the transcriptional (mRNA) and translational (protein) levels.
Main Methods:
- Rat myocardial cell line H9c2(2-1) was treated with lovastatin (100 nmol/L) for 24 hours and five days.
- Quantitative real-time polymerase chain reaction (Q-RT-PCR) was used to assess mRNA levels.
- Immunoblotting was employed to determine protein levels.
Main Results:
- Lovastatin significantly increased LDHA mRNA levels after 24 hours and five days.
- LDHB mRNA levels were unchanged after 24 hours but significantly decreased after five days.
- After five days, lovastatin significantly upregulated LDHA protein and downregulated LDHB protein.
Conclusions:
- Lovastatin exerts differential effects on LDHA and LDHB gene expression and protein levels.
- These distinct molecular changes may indicate novel pharmacological mechanisms of lovastatin.
- Further research is warranted to explore these implications in cardiovascular health.
Background:
Lactate dehydrogenase (LDH) is a crucial regulator of energy metabolism in many organs including the heart. Lovastatin is widely used in prevention and treatment of coronary heart disease and is a drug with substantial metabolic influences. Our study aimed to determine the activities of the lactate dehydrogenase A and B (LDHA and LDHB) genes following lovastatin treatment.
Methods:
The rat myocardial cell line H9c2(2-1) in culture was exposed to 100 nmol/L lovastatin for 24 hours or for five days. The functions of the LDHA and LDHB genes were examined at the transcriptional (mRNA) level with quantitative real-time polymerase chain reaction (Q-RT-PCR), and at the translational (protein) level with immunoblotting.
Results:
When compared with control levels, the LDHA mRNA went up by (151.65 ± 16.72)% (P = 0.0132) after 24 hours and by (175.28 ± 56.54)% (P = 0.0366) after five days of lovastatin treatment. Although 24 hours of lovastatin treatment had no significant effects on LDHB mRNA levels, when the treatment was extended to five days, LDHB mRNA levels were significantly down-regulated to (63.65 ± 15.21)% of control levels (P = 0.0117). After 24 hours of treatment with lovastatin, there were no significant changes in protein levels of either LDHA or LDHB. When treatment time was extended to five days, the protein levels of LDHA were up-regulated by (148.65 ± 11.81)% (P = 0.00969), while the protein levels of LDHB were down-regulated to (64.91 ± 5.47)% of control levels (P = 0.0192).
Conclusions:
Lovastatin affects gene activities of LDHA and LDHB differently, which may reveal novel pharmacological effects of lovastatin.
