Biochemical and biophysical research communications
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Biochem. Biophys. Res. Commun. · Feb 2015
Prolonging the survival of Tsc2 conditional knockout mice by glutamine supplementation.
The genetic disease tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by loss of function mutations in either TSC1 (hamartin) or TSC2 (tuberin), which serve as negative regulators of mechanistic target of rapamycin complex 1 (mTORC1) activity. TSC patients exhibit developmental brain abnormalities and tuber formations that are associated with neuropsychological and neurocognitive impairments, seizures and premature death. Mechanistically, TSC1 and TSC2 loss of function mutations result in abnormally high mTORC1 activity. ⋯ Our results show that glutamine can reduce phosphorylation of S6 and S6 kinase, surrogate indicators of mTORC1 activity, in both deprived and non-deprived cells, although higher concentrations were required for non-deprived cultures. When administered orally to TSC2 knockout mice, glutamine reduced S6 phosphorylation in the brain and significantly prolonged their lifespan. Taken together, these results suggest that glutamine supplementation can be used as a potential treatment for TSC.
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Biochem. Biophys. Res. Commun. · Feb 2015
Midazolam inhibits the formation of amyloid fibrils and GM1 ganglioside-rich microdomains in presynaptic membranes through the gamma-aminobutyric acid A receptor.
Recent studies have suggested that a positive correlation exists between surgical interventions performed under general anesthesia and the risk of developing Alzheimer's disease (AD) in the late postoperative period. It has been reported that amyloid β-protein (Αβ) fibrillogenesis, which is closely related to AD, is accelerated by exposure to anesthetics. However, the mechanisms underlying these effects remain uncertain. ⋯ In addition, midazolam suppressed GM1-induced fibril formation in a cell-free system. Moreover, midazolam inhibited the formation of Αβ assemblies in synaptosomes isolated from aged mouse brains. These finding suggested that midazolam has direct and indirect inhibitory effects on Αβ fibrillogenesis.
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Biochem. Biophys. Res. Commun. · Jan 2015
Eicosapentaenoic acid (EPA) induced apoptosis in HepG2 cells through ROS-Ca(2+)-JNK mitochondrial pathways.
Eicosapentaenoic acid (EPA), a well-known dietary n-3 PUFAS, has been considered to inhibit proliferation of tumor cells. However, the molecular mechanism related to EPA-induced liver cancer cells apoptosis has not been reported. In this study, we investigated the effect of EPA on HepG2 cells proliferation and apoptosis mechanism through mitochondrial pathways. ⋯ Western blotting results showed that EPA elevated the phosphorylation status of JNK, processes associated with the ROS generation. Simultaneously, the apoptosis induced by EPA was related to release of cytochrome C from mitochondria to cytoplasm through the MPTP and activation of caspase-9 and caspase-3. These results suggest that EPA induces apoptosis through ROS-Ca(2+)-JNK mitochondrial pathways.
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Biochem. Biophys. Res. Commun. · Jan 2015
Genetic variants of vitamin D receptor and susceptibility to ischemic stroke.
Vitamin D receptor (VDR) is a potential candidate for cardiovascular disease. To date the genetic association of VDR with ischemic stroke has not been explored. In the present study we aimed to evaluate the association between VDR gene variants and ischemic stroke in Asian Indian population. ⋯ In the present study we could associate the only known functional polymorphism of VDR i.e., Fok I, with ischemic stroke in a gender specific manner. Adjustment with lipid variables was found to attenuate this association indicating that impaired lipid metabolism may be the underlying mechanism of action of this polymorphism which leads to an increase in the risk of ischemic stroke. Further larger scale validations in other population are warranted in other population.
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Biochem. Biophys. Res. Commun. · Dec 2014
An extract from medical leech improve the function of endothelial cells in vitro and attenuates atherosclerosis in ApoE null mice by reducing macrophages in the lesions.
Medicinal leech has been widely used as a traditional Chinese medicine in cardiovascular diseases. However, its pharmaceutical effect is not fully revealed. The goal of this study was to determine whether a leech extract has the effect of anti-atherosclerosis in ApoE −/− mice and the mechanism of this effect. ⋯ Leech extract could obviously attenuate the area of atherosclerosis lesion in ApoE −/− mice. And this effect is dose dependent. The effect is mainly a result of reduced invasion of monocyte in artery walls by blocking NF-κB translocation.