[Show abstract][Hide abstract] ABSTRACT: Apoptosis repressor with caspase recruitment domain (ARC) is highly involved in apoptosis induced by oxidative stress or ischaemia/reperfusion injury. Furthermore, even though the exact mechanism is still unknown, some studies suggest that exogenous ARC also possesses anti-apoptotic ability. The study investigated whether mouse-derived ARC acquires anti-apoptotic ability and the pathway of regulation in chick embryo cardiomyocytes. To evaluate whether mouse-derived ARC can inhibit chick embryo cardiomyocyte apoptosis induced by hydrogen peroxide, recombinant pcDNA3.1/ARC plasmid was acquired and transfected into chick embryo cardiomyocytes. ARC-related gene (caspase-2, caspase-8, caspase-3, and caspase-9, cytochrome C, bcl-2, and XIAP) mRNA and protein expression levels were detected by real-time polymerase chain reaction and western blotting, respectively. Here we demonstrate that hydrogen peroxide induced apoptosis in chick embryo cardiomyocytes in a time-dependent manner and that this effect could be suppressed by mouse-derived ARC expression. Moreover, unlike endogenous ARC, exogenous ARC was exclusively expressed in the cytoplasm and down-regulated caspase-2, caspase-8, and caspase-3, bcl-2, and XIAP gene expression levels. However, only caspase-3 protein levels were decreased. In addition, threonine 149 phosphorylation by CK2 was required for exogenous ARC to exert an anti-apoptotic effect in chicken embryo cardiomyocytes and suggested exogenous ARC may in part share the same pathway of regulation with endogenous ARC. These results indicate that mouse-derived ARC plays an important role in protection of chick embryo cardiomyocytes against oxidative stress apoptosis by inhibiting caspase-3 mRNA and protein expression levels.
[Show abstract][Hide abstract] ABSTRACT: It is believed that ascitic broilers die of right heart failure caused by pulmonary hypertension, but the underlying mechanisms of right heart failure are unknown. However, recent studies have shown that reactive oxygen species have the ability to damage heart cells. This study aimed to determine the changes of reactive oxygen species in serum and plasma, and the effect of this variation on myocardial cells during broiler ascites. We used hypoxia and a low-temperature method to induce broiler ascites in the fast-growing group. For controls, we treated a slow-growing group of broilers with 70% restricted feeding under the same circumstances as the fast-growing group. The results showed that hypoxia is a more effective and better way to induce broiler ascites than a low-temperature environment and high growth rate. In addition, reactive oxygen species levels were significantly increased in the fast-growing group compared with those in the slow-growing group. This significant increase in reactive oxygen species resulted in myocardial cell apoptosis in the fast-growing group. Our results suggest that cardiomyocyte apoptosis caused by increased reactive oxygen species levels of ascitic broilers is one of the most important reasons for causing heart failure.
No preview · Article · Jan 2012 · Pakistan Veterinary Journal
[Show abstract][Hide abstract] ABSTRACT: Integrins alphavbeta3 and alphavbeta5 are overexpressed in angiogenic tumor endothelial cells and malignant tumor cells, making them attractive targets for cancer therapy. In this study, an integrin alphavbeta3 and alphavbeta5 binding tripeptide, RGD (Arg-Gly-Asp), was conjugated with the surface of poly(ethylene glycol)-block-poly(D,L-lactide) (PEG-PLA) micelles. A lipophilic fluorescent probe, DiI, was loaded into both the nontargeted methoxy PEG-PLA (mPEG-PLA) micelles and the targeted RGD-modified PEG-PLA micelles. The DiI-loaded targeted micelles had a size of 24.2 nm. The targeted micelles were stable in phosphate buffered saline and exhibited a negligible leakage in culture medium. Transmission electron microscopy analysis showed that targeted micelles were spherical in shape. Cell uptake of DiI-labeled targeted micelles by human umbilical vein endothelial cells and melanoma B16 cells was investigated by spectrophotofluorometry and confocal microscopy techniques. Results revealed that RGD-modified micelles significantly facilitated the intracellular delivery of the encapsulated agents via integrin-mediated endocytosis. This study suggests that RGD-modified PEG-PLA micelles are promising drug carriers for targeted delivery to both angiogenic tumor endothelial cells and tumor cells and that the targeted micelles may be attractive carriers for combination cancer therapy against both targets.
No preview · Article · Aug 2009 · Journal of Drug Targeting
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to characterize the levels of free radicals in serum and antioxidase activity after microcapsules were implanted into the subcutaneous space of mice. cell viability was evaluated using ao/Eb staining. serum free radicals, malondialdehyde and superoxide dismutase levels were evaluated by colorimetry analysis. the mice were divided into three groups: saline injection group (n=15), empty microcapsules injected group (n=21), encapsulated cells injected group (n=21). cell viability and serum analysis were executed at 1, 4 and 7 days post-implantation. Hydrogen peroxide and malondialdehyde levels initially increased in the recipients of the empty microcapsules, before decreasing to the basal level. However, in mice receiving the encapsulated cells, the levels were higher at the end of study. nitric oxide and superoxide dismutase increased after the implantation of microcapsules with or without the bHK-21 cells, but were not changed in response to the saline injection. the viability of the encapsulated cells was high in vivo, although some microcapsules had broken by 7 days post-implantation. these results suggest that nitric oxide plays a role in the specific response to microcapsules. the levels of free radicals rapidly increased immediately following microcapsule transplantation, but they caused only slight cellular damage before the microencapsulated cells were exposed.
No preview · Article · May 2009 · The International journal of artificial organs