Abstract
The heart is unable to synthesize l-carnitine and is strictly dependent on the l-carnitine provided by the blood stream; however, additional studies are needed to better understand the mechanism of l-carnitine supplementation to the heart. The aim of this study was to evaluate the effects of l-carnitine on angiotensin II (Ang II)-induced cardiac fibroblast proliferation and to explore its intracellular mechanism(s). Cultured rat cardiac fibroblasts were pretreated with l-carnitine (1-30 mM) then stimulated with Ang II (100 nM). Ang II increased fibroblast proliferation and endothelin-1 expression, which were partially inhibited by l-carnitine. l-Carnitine also attenuated Ang II-induced NADPH oxidase activity, reactive oxygen species formation, extracellular signal-regulated kinase phosphorylation, activator protein-1-mediated reporter activity and sphingosine-1-phosphate generation. In addition, l-carnitine increased prostacyclin (PGI2) generation in cardiac fibroblasts. siRNA transfection of PGI2 synthase significantly reduced l-carnitine-induced PGI2 and its anti-proliferation effects on cardiac fibroblasts. Furthermore, blockading potential PGI2 receptors, including immunoprecipitation (IP) receptors and peroxisome proliferator-activated receptors alpha (PPAR?) and delta , revealed that siRNA-mediated blockage of PPAR? considerably reduced the anti-proliferation effect of l-carnitine. In summary, these results suggest that l-carnitine attenuates Ang II-induced effects (including NADPH oxidase activation, sphingosine-1-phosphate generation and cell proliferation) in part through PGI2 and PPAR?-signaling pathways.
| Original language | English |
|---|---|
| Pages (from-to) | 580-588 |
| Number of pages | 9 |
| Journal | Journal of Nutritional Biochemistry |
| Volume | 21 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jul 2010 |
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Keywords
- Angiotensin II
- Cardiac fibroblasts
- L-carnitine
- NADPH oxidase
- Prostacyclin
- Sphingosine-1-phosphate
ASJC Scopus subject areas
- Biochemistry
- Clinical Biochemistry
- Molecular Biology
- Endocrinology, Diabetes and Metabolism
- Nutrition and Dietetics
- Medicine(all)
Cite this
L-Carnitine attenuates angiotensin II-induced proliferation of cardiac fibroblasts : Role of NADPH oxidase inhibition and decreased sphingosine-1-phosphate generation. / Chao, Hung Hsin; Chen, Cheng Hsien; Liu, Ju Chi; Lin, Jia Wei; Wong, Kar Lok; Cheng, Tzu-Hurng.
In: Journal of Nutritional Biochemistry, Vol. 21, No. 7, 07.2010, p. 580-588.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - L-Carnitine attenuates angiotensin II-induced proliferation of cardiac fibroblasts
T2 - Role of NADPH oxidase inhibition and decreased sphingosine-1-phosphate generation
AU - Chao, Hung Hsin
AU - Chen, Cheng Hsien
AU - Liu, Ju Chi
AU - Lin, Jia Wei
AU - Wong, Kar Lok
AU - Cheng, Tzu-Hurng
PY - 2010/7
Y1 - 2010/7
N2 - The heart is unable to synthesize l-carnitine and is strictly dependent on the l-carnitine provided by the blood stream; however, additional studies are needed to better understand the mechanism of l-carnitine supplementation to the heart. The aim of this study was to evaluate the effects of l-carnitine on angiotensin II (Ang II)-induced cardiac fibroblast proliferation and to explore its intracellular mechanism(s). Cultured rat cardiac fibroblasts were pretreated with l-carnitine (1-30 mM) then stimulated with Ang II (100 nM). Ang II increased fibroblast proliferation and endothelin-1 expression, which were partially inhibited by l-carnitine. l-Carnitine also attenuated Ang II-induced NADPH oxidase activity, reactive oxygen species formation, extracellular signal-regulated kinase phosphorylation, activator protein-1-mediated reporter activity and sphingosine-1-phosphate generation. In addition, l-carnitine increased prostacyclin (PGI2) generation in cardiac fibroblasts. siRNA transfection of PGI2 synthase significantly reduced l-carnitine-induced PGI2 and its anti-proliferation effects on cardiac fibroblasts. Furthermore, blockading potential PGI2 receptors, including immunoprecipitation (IP) receptors and peroxisome proliferator-activated receptors alpha (PPAR?) and delta , revealed that siRNA-mediated blockage of PPAR? considerably reduced the anti-proliferation effect of l-carnitine. In summary, these results suggest that l-carnitine attenuates Ang II-induced effects (including NADPH oxidase activation, sphingosine-1-phosphate generation and cell proliferation) in part through PGI2 and PPAR?-signaling pathways.
AB - The heart is unable to synthesize l-carnitine and is strictly dependent on the l-carnitine provided by the blood stream; however, additional studies are needed to better understand the mechanism of l-carnitine supplementation to the heart. The aim of this study was to evaluate the effects of l-carnitine on angiotensin II (Ang II)-induced cardiac fibroblast proliferation and to explore its intracellular mechanism(s). Cultured rat cardiac fibroblasts were pretreated with l-carnitine (1-30 mM) then stimulated with Ang II (100 nM). Ang II increased fibroblast proliferation and endothelin-1 expression, which were partially inhibited by l-carnitine. l-Carnitine also attenuated Ang II-induced NADPH oxidase activity, reactive oxygen species formation, extracellular signal-regulated kinase phosphorylation, activator protein-1-mediated reporter activity and sphingosine-1-phosphate generation. In addition, l-carnitine increased prostacyclin (PGI2) generation in cardiac fibroblasts. siRNA transfection of PGI2 synthase significantly reduced l-carnitine-induced PGI2 and its anti-proliferation effects on cardiac fibroblasts. Furthermore, blockading potential PGI2 receptors, including immunoprecipitation (IP) receptors and peroxisome proliferator-activated receptors alpha (PPAR?) and delta , revealed that siRNA-mediated blockage of PPAR? considerably reduced the anti-proliferation effect of l-carnitine. In summary, these results suggest that l-carnitine attenuates Ang II-induced effects (including NADPH oxidase activation, sphingosine-1-phosphate generation and cell proliferation) in part through PGI2 and PPAR?-signaling pathways.
KW - Angiotensin II
KW - Cardiac fibroblasts
KW - L-carnitine
KW - NADPH oxidase
KW - Prostacyclin
KW - Sphingosine-1-phosphate
UR - http://www.scopus.com/inward/record.url?scp=77953812861&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953812861&partnerID=8YFLogxK
U2 - 10.1016/j.jnutbio.2009.03.003
DO - 10.1016/j.jnutbio.2009.03.003
M3 - Article
VL - 21
SP - 580
EP - 588
JO - Journal of Nutritional Biochemistry
JF - Journal of Nutritional Biochemistry
SN - 0955-2863
IS - 7
ER -