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Lin P.-P.,Providence University | Hsieh Y.-M.,Providence University | Kuo W.-W.,University of Science and Technology of China | Lin C.-C.,Armed Forces General Hospital | And 7 more authors.
International Journal of Molecular Medicine | Year: 2012

Cardiovascular hypertrophy is a common feature of hypertension and an important risk factor for heart damage. The regression of cardiovascular hypertrophy is currently considered an important therapeutic target in reducing the omplications of hypertension. The aim of this study was to investigate the inhibition of cardiac hypertrophy by probiotic-fermented purple sweet potato yogurt (PSPY) with high ã-aminobutyric acid (GABA) content in spontaneously hypertensive rat (SHR) hearts. Six-week-old male SHRs were separated randomly and equally into 4 experimental groups: sterile water, captopril and 2 PSPY groups with different doses (10 and 100%) for 8 weeks. The changes in myocardial architecture and key molecules of the hypertrophy-related pathway in the excised left ventricle from these rats were determined by histopathological analysis, hematoxylin and eosin staining and western blot analysis. Abnormal myocardial architecture and enlarged interstitial spaces observed in the SHRs were significantly decreased in the captopril and PSPY groups compared with the sterile water group. Moreover, the increases in atrial natriuretic peptide, B-type natriuretic peptide, phosphorilated protein kinase Cα and calmodulin-dependent protein kinase II levels in the left ventricle were accompanied by hypertension and increases in phosphorylated extracellular signal-regulated kinase 5 activities with enhanced cardiac hypertrophy. However, the protein levels of the hypertrophic-related pathways were completely reversed by the administration of PSPY. PSPY may repress the activation of ANP and BNP which subsequently inhibit the dephosphorylation of the nuclear factor of activated T-cells, cytoplasmic 3 and ultimately prevent the progression of cardiac hypertrophy. Source

Feng C.-C.,China Medical University at Taichung | Lin C.-C.,Armed Forces General Hospital | Lai Y.-P.,China Medical University at Taichung | Chen T.-S.,China Medical University at Taichung | And 7 more authors.
Growth Factors | Year: 2016

The HIF-1α transcriptional factor and the BH-3 only protein BNIP3 are known to play fundamental roles in response to hypoxia. The objective of this research is to investigate the molecular mechanisms and the correlation of HIF-1α, BNIP3 and IGFBP-3 in hypoxia-induced cardiomyocytes injuries. Heart-derived H9c2 cells and neonatal rat ventricular myocytes (NRVMs) were incubated in normoxic or hypoxic conditions. Hypoxia increased HIF-1α expression and activated the downstream BNIP3 and IGFBP-3 thereby triggered mitochondria-dependent apoptosis. Moreover, IGF1R/PI3K/Akt signaling was attenuated by HIF-1α-dependent IGFBP-3 expression to enhance hypoxia-induced apoptosis. Autophagy suppression with 3-methyladenine or siATG5 or siBeclin-1 significantly decreased myocardial apoptosis under hypoxia. Knockdown of FoxO3a or BNIP3 significantly abrogated hypoxia-induced autophagy and mitochondria-dependent apoptosis. Moreover, prolonged-hypoxia induced HIF-1α stimulated BNIP3 and enhanced IGFBP-3 activation to inhibit IGF1R/PI3K/Akt survival pathway and mediate mitochondria-dependent cardiomyocyte apoptosis. HIF-1α and FoxO3a blockage are sufficient to annul the change of excessive hypoxia of hearts. © 2016 Informa UK Limited, trading as Taylor & Francis Group. Source

Lin K.-H.,China Medical University at Taichung | Kuo C.-H.,University of Taipei | Kuo W.-W.,China Medical University at Taichung | Ho T.-J.,China Medical University at Taichung | And 8 more authors.
Journal of Cellular Biochemistry | Year: 2015

The insulin-like growth factor-II/mannose 6-phosphate receptor (IGF2R) over-expression correlates with heart disease progression. The IGF2R is not only an IGF2 clearance receptor, but it also triggers signal transduction, resulting in cardiac hypertrophy, apoptosis and fibrosis. The present study investigated the nuclear factor IL-3 (NFIL3), a transcription factor of the basic leucine zipper superfamily, and its potential pro-survival effects in cardiomyocytes. NFIL3 might play a key role in heart development and act as a survival factor in the heart, but the regulatory mechanisms are still unclear. IGF2 and IGF2R protein expression were highly increased in rat hearts subjected to hemorrhagic shock. IGF2R protein expression was also up-regulated in H9c2 cells exposed to hypoxia. Over-expression of NFIL3 in H9c2 cardiomyoblast cells inhibited the induction of hypoxia-induced apoptosis and down-regulated IGF2R expression levels. Gel shift assay, double-stranded DNA pull-down assay and chromatin immune-precipitation analyses indicated that NFIL3 binds directly to the IGF2R promoter region. Using a luciferase assay, we further observed NFIL3 repress IGF2R gene promoter activity. Our results demonstrate that NFIL3 is an important negative transcription factor, which through binding to the promoter of IGF2R, suppresses the apoptosis induced by IGF2R signaling in H9c2 cardiomyoblast cells under hypoxic conditions. J. Cell. Biochem. 116: 1113-1120, 2015. © 2015 Wiley Periodicals, Inc. Source

Huang C.-Y.,China Medical University at Taichung | Huang C.-Y.,Asia University, Taiwan | Kuo W.-W.,China Medical University at Taichung | Shibu M.A.,China Medical University at Taichung | And 8 more authors.
American Journal of Chinese Medicine | Year: 2014

Factors that enhance the intrinsic growth potential of neurons play a major role in the regeneration and repair of adult neurons following an injury. Fibroblast growth factor (FGF-2) is one of the key players in the origin and growth of neuronal and glial cells through autocrine and paracrine signaling. Water extract of Citrus medica var. sarcodactylis (fingered citron, foshou), which is been used effectively as a Chinese herbal medicine, was found to activate the FGF-2 promoter in transgenic luciferase expression models. Foshou treatment on Schwann cells (RSC96) transfected with luciferase reporter plasmid under a FGF-2 promoter was found to induce the FGF-2 promoter and showed enhanced luciferase expression. The FGF-2 expression was accompanied with an increase in the expression of proteins involved in cell migration and cell proliferation in a dose dependent manner. Therefore, foshou potentially enhances nerve regeneration by inducing the Schwann cell proliferation and migration. © 2014 World Scientific Publishing Company. Source

Ju D.-T.,National Defense Medical Center | Ho T.-J.,China Medical University at Taichung | Paul C.R.,China Medical University at Taichung | Kuo C.-H.,Laboratory of Exercise Biochemistry | And 5 more authors.
American Journal of Chinese Medicine | Year: 2015

Alpinia oxyphylla MIQ (Alpinate Oxyphyllae Fructus, AOF) is an important traditional Chinese medicinal herb whose fruits is widely used to prepare tonics and is used as an aphrodisiac, anti salivary, anti diuretic and nerve-protective agent. Protocatechuic acid (PCA), a simple phenolic compound was isolated from the kernels of AOF. This study investigated the role of PCA in promoting neural regeneration and the underlying molecular mechanisms. Nerve regeneration is a complex physiological response that takes place after injury. Schwann cells play a crucial role in the endogenous repair of peripheral nerves due to their ability to proliferate and migrate. The role of PCA in Schwann cell migration was determined by assessing the induced migration potential of RSC96 Schwann cells. PCA induced changes in the expression of proteins of three MAPK pathways, as determined using Western blot analysis. In order to determine the roles of MAPK (ERK1/2, JNK, and p38) pathways in PCA-induced matrix-degrading proteolytic enzyme (PAs and MMP2/9) production, the expression of several MAPK-associated proteins was analyzed after siRNA-mediated inhibition assays. Treatment with PCA-induced ERK1/2, JNK, and p38 phosphorylation that activated the downstream expression of PAs and MMPs. PCA-stimulated ERK1/2, JNK and p38 phosphorylation was attenuated by individual pretreatment with siRNAs or MAPK inhibitors (U0126, SP600125, and SB203580), resulting in the inhibition of migration and the uPA-related signal pathway. Taken together, our data suggest that PCA extract regulate the MAPK (ERK1/2, JNK, and p38)/PA (uPA, tPA)/MMP (MMP2, MMP9) mediated regeneration and migration signaling pathways in Schwann cells. Therefore, PCA plays a major role in Schwann cell migration and the regeneration of damaged peripheral nerve. © 2015 World Scientific Publishing Company & Institute for Advanced Research in Asian Science and Medicine. Source

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