Ghrelin prevents doxorubicin-induced cardiotoxicity through TNF-alpha/NF-κB pathways and mitochondrial protective mechanisms

Xu, Zuo-Feng; Shi-qing, Lin; Wu, Weikang; Tan, Hongmei; Zhi, Wang; Cheng, Chao; Lu, Lihe; Zhang, Xuanhong

doi:10.1016/j.tox.2008.02.018

Cited by 108 publications

(67 citation statements)

References 44 publications

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“…HUVECs were cultured in 6-well plates until reaching confluence and then pretreated with various concentrations of geniposide for different lengths of time. Immunofluorescence microscopy Translocation of NF-κB p65 from the cytoplasm to the nucleus was determined using the Cellular NF-κB Translocation Kit according to manufacturer's instructions [23] . Briefly, HUVECs were cultured in 24-well plates until reaching confluence and then pretreated with 20 μg/mL geniposide for 45 min.…”

Section: Measurement Of Adhesion Moleculesmentioning

confidence: 99%

Geniposide inhibits high glucose-induced cell adhesion through the NF-κB signaling pathway in human umbilical vein endothelial cells

Wang

Xü

et al. 2010

Acta Pharmacol Sin

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Aim: To investigate whether geniposide, an iridoid glucoside extracted from gardenia jasminoides ellis fruits, inhibits cell adhesion to human umbilical vein endothelial cells (HUVECs) induced by high glucose and its underlying mechanisms. Methods: HUVECs were isolated from human umbilical cords and cultured. The adhesion of monocytes to HUVECs was determined using fluorescence-labeled monocytes. The mRNA and protein levels of vascular cell adhesion molecule-1 (VCAM-1) and endothelial selectin (E-selectin) were measured using real-time RT-PCR and ELISA. Reactive oxygen species (ROS) production was measured using a fluorescent probe. The amounts of nuclear factor-kappa B (NF-κB) and inhibitory factor of NF-κB (IκB) were determined using Western blot analysis. The translocation of NF-κB from the cytoplasm to the nucleus was determined using immunofluorescence. Results: Geniposide (10-20 µmol/L) inhibited high glucose (33 mmol/L)-induced adhesion of monocytes to HUVECs in a dose-dependent manner. This compound (5-40 µmol/L) also inhibited high glucose-induced expression of VCAM-1 and E-selectin at the gene and protein levels. Furthermore, geniposide (5-20 µmol/L) decreased ROS production and prevented IκB degradation in the cytoplasm and NF-κB translocation from the cytoplasm to the nucleus in HUVECs. Conclusion: Geniposide inhibits the adhesion of monocytes to HUVECs and the expression of CAMs induced by high glucose, suggesting that the compound may represent a new treatment for diabetic vascular injury. The mechanism underlying this inhibitory effect may be related to the inhibition of ROS overproduction and NF-κB signaling pathway activation by geniposide.

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Section: Measurement Of Adhesion Moleculesmentioning

confidence: 99%

Geniposide inhibits high glucose-induced cell adhesion through the NF-κB signaling pathway in human umbilical vein endothelial cells

Wang

Xü

et al. 2010

Acta Pharmacol Sin

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“…As a transcription factor affecting potentially the expression of many genes, nuclear factor kappa B (NFκB) may favor cell survival by up-regulating gene products with anti-apoptotic properties or down-regulating pro-apoptotic factors (Xu et al, 2008). The up-regulation of FLIP expression following NFκB activation and its involvement in preventing apoptosis has been observed after stimulation by CD40L, lipopolysaccharide, and TNF (Xiao et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Toll-like receptor 9-mediated inhibition of apoptosis occurs through suppression of FoxO3a activity and induction of FLIP expression

et al. 2010

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“…It is thus possible that ghrelin may be acting directly on the heart and vasculature rather than it effects being mediated by growth hormone (GH) (11). As an important autocrine/paracrine factor, ghrelin has various cardiovascular effects, including inotropic action, vasodilatation, anti-apoptosis, and antiinflammation (12)(13)(14)(15)(16), that indicate that ghrelin may maintain cardiovascular homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Ghrelin reduces rat myocardial calcification induced by nicotine and vitamin D3 in vivo

Wang

Jiang²,

Tang³

et al. 2011

Int J Mol Med

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Abstract. Ghrelin, a newly discovered bioactive peptide, initially was identified as a strong stimulant for the release of growth hormone (GH) and that has improved cardiac function in patients suffering from end-stage chronic heart failure. Increasing evidence has demonstrated that ghrelin may have myocardial protective effects. However, the role of ghrelin in the pathogenesis of cardiovascular diseases remains unclear. In this study, an in vivo model of rat myocardial calcification induced by vitamin D3 and nicotine was used to study the possible mechanism in the regulatory action of ghrelin on the calcified myocardium. Calcification increased total Ca 2+ content and 45 Ca 2+ deposition in the myocardium and alkaline phosphatase (ALP) activation in the plasma. Compared with the control group, ghrelin mRNA expression was up-regulated and the myocardium calcium content was significantly increased in vitamin D3 and nicotine-treated rats. Rats were subcutaneously injected with 1 or 10 nmol/kg ghrelin. Rats treated with both low-and high-dose ghrelin decreased total Ca 2+ content and 45 Ca 2+ deposition in cardiac muscle and inhibited ALP activation in the myocardium and plasma, in a concentration-dependent manner. In addition, osteopontin (OPN) mRNA expression significantly decreased and that of endothelin (ET-1) significantly increased with myocardial calcification. Ghrelin treatment increased OPN expression at the mRNA level and reduced ET-1 mRNA expression in a dose-dependent manner. These results indicate that exogenous administration with ghrelin attenuates myocardial calcification induced by nicotine and vitamin D3, and that the possible mechanism is via the ghrelin-induced increase in the OPN mRNA levels and decrease in the ET-1 mRNA expression in the myocardium.

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Ghrelin prevents doxorubicin-induced cardiotoxicity through TNF-alpha/NF-κB pathways and mitochondrial protective mechanisms

Cited by 108 publications

References 44 publications

Geniposide inhibits high glucose-induced cell adhesion through the NF-κB signaling pathway in human umbilical vein endothelial cells

Geniposide inhibits high glucose-induced cell adhesion through the NF-κB signaling pathway in human umbilical vein endothelial cells

Toll-like receptor 9-mediated inhibition of apoptosis occurs through suppression of FoxO3a activity and induction of FLIP expression

Ghrelin reduces rat myocardial calcification induced by nicotine and vitamin D3 in vivo

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