The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
MicroRNA-195 promotes palmitate-induced apoptosis in cardiomyocytes by down-regulating Sirt1
Abstract
AIMS: Free fatty acids induce apoptosis in cardiomyocytes, which is implicated in lipotoxic cardiomyopathy. However, the underlying mechanisms remain not fully understood. MicroRNAs (miRNAs) are non-coding small RNAs that control gene expression at the post-transcriptional level. Dysregulated miRNAs have been shown to be involved in heart diseases. This study was to examine whether miR-195 regulates palmitate-induced cardiomyocyte apoptosis by targeting Sirt1, a known anti-apoptotic protein. METHODS AND RESULTS: In cultured neonatal mouse cardiomyocytes, palmitate up-regulated miR-195 expression, increased reactive oxygen species (ROS) production, and induced apoptosis as determined by up-regulation of caspase-3 activity and DNA fragmentation. Inhibition of miR-195 decreased ROS production and apoptosis in palmitate-stimulated cardiomyocytes. In contrast, a miR-195 mimic enhanced palmitate-induced ROS production and apoptosis. The induction of miR-195 correlated with a reduction in Sirt1 and Bcl-2. We further showed that miR-195 targeted and inhibited Sirt1 expression through two target sites located in the 3' un-translational region of Sirt1 mRNA. In concordance, inhibition of miR-195 increased Sirt1 protein in cardiomyocytes whereas the miR-195 mimic reduced it. Activation of Sirt1 or overexpression of Bcl-2 inhibited palmitate-induced apoptosis. On the other hand, inhibition of Sirt1 enhanced apoptosis. The inhibitory effect of Sirt1 on apoptosis was associated with a reduction in ROS. CONCLUSIONS: This study demonstrates a pro-apoptotic role of miR-195 in cardiomyocytes and identifies Sirt1 as a direct target of miR-195. The effect of miR-195 on apoptosis is mediated through down-regulation of Sirt1 and Bcl-2 and ROS production. Thus, miR-195 may be a new therapeutic target for lipotoxic cardiomyopathy.
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Cites
The functions of animal microRNAs
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Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase
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Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction
Haigis, M. C., & Guarente, L. P. (2006) · Genes & Development · doi:10.1101/gad.1467506 · Cited by 1,295
Lipotoxic heart disease in obese rats: Implications for human obesity
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Self-citationSirtuins in aging and age-related disease
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Cited by
Szeto, H. H. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12461 · Cited by 548
Regulation of SIRT1 in aging: Roles in mitochondrial function and biogenesis
Yuan, Y., Cruzat, V. F., Newsholme, P., Cheng, J., Chen, Y., & Lu, Y. (2016) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2016.02.003 · Cited by 299
Negative regulation of inflammation by SIRT1
Xie, J., Zhang, X., & Zhang, L. (2013) · Pharmacological Research · doi:10.1016/j.phrs.2012.10.010 · Cited by 234
Sirtuin‐dependent epigenetic regulation in the maintenance of genome integrity
Bosch‐Presegué, L., & Vaquero, A. (2015) · The FEBS Journal · doi:10.1111/febs.13053 · Cited by 132
Saturated free fatty acids induce cholangiocyte lipoapoptosis
Natarajan, S. K., Ingham, S. A., Mohr, A. M., Wehrkamp, C. J., Ray, A., Roy, S., Cazanave, S. C., Phillippi, M. A., & Mott, J. L. (2014) · Hepatology · doi:10.1002/hep.27175 · Cited by 62
Metadata
- Authors
- Zhu, H., Yang, Y., Wang, Y., Li, J., Schiller, P. W., & Peng, T.
- Venue
- Cardiovascular Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-05-27
- Volume
- 92
- Issue
- 1
- Pages
- 75-84
- ISSN
- 0008-6363 (ISSN-L)
- 1755-3245
- OpenAlex
- W2170910763
- Cited by
- 188
- References
- 11
- FWCI
- 5.30
- Type
- journal article
- Language
- en
- Open access
- closed
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