Low molecular weight guluronate prevents TNF-α-induced oxidative damage and mitochondrial dysfunction in C2C12 skeletal muscle cells.

Muscle wasting is associated with a variety of chronic or inflammatory disorders. Evidence suggests that inflammatory cytokines play a vital role in muscle inflammatory pathology and this may result in oxidative damage and mitochondrial dysfunction in skeletal muscle. In our study, we used microwave degradation to prepare a water-soluble low molecular weight guluronate (LMG) of 3000 Da from Fucus vesiculosus obtained from Canada, the Atlantic Ocean. We demonstrated the structural characteristics, using HPLC, FTIR and NMR of LMG and investigated its effects on oxidative damage and mitochondrial dysfunction in C2C12 skeletal muscle cells induced by tumor necrosis factor alpha (TNF-α), a cell inflammatory cytokine. The results indicated that LMG could alleviate mitochondrial reactive oxygen species (ROS) production, increase the activities of antioxidant enzymes (GSH and SOD), promote mitochondrial membrane potential (MMP) and upregulate the expression of mitochondrial respiratory chain protein in TNF-α-induced C2C12 cells. LMG supplement also increased the mitochondrial DNA copy number and mitochondrial biogenesis related genes in TNF-α-induced C2C12 cells. LMG may exert these protective effects through the nuclear factor kappa B (NF-κB) signaling pathway. These suggest that LMG is capable of protecting TNF-α-induced C2C12 cells against oxidative damage and mitochondrial dysfunction.

[The active expression of CenpB, a constitutive protein in the centromeres of chromosomes, in breast cancer tissues].

At present, a point that cell biologists and medicine scientists focus their close attention on is the mechanisms of cell proliferation and carceration. Breast cancer, one of the frequently occurring cancers, is often been studied intensively. Centromere constitutive molecules, related to various regulatory factors, play an important role in cell proliferation check point regulation. Cell cycle engine molecules, oncogenes, anti-oncogenes and other molecules conform a cell proliferation network. The basic courses of all tumors are associated to this network. However, there are still many problems to be resolved in the analyses of cancer related genes which cause tumors and tumor gene markers. In the current study, using Northern blot, 31 samples of breast cancer tissues and their normal (not cancerous) tissues a little far away from them in the same individuals showed that, in the majority of the tests (87.1%), the mRNA of centromere protein CenpB over expressed in breast cancer tissues, and moreover, tissue in situ hybridization also revealed that all of the CenpB-over-expressed cancer tissues, having identified with Northern blot, over expressed CenpB mRNA. Analyzing the same samples by means of Western blot, the result was highly consistent to the studies in the RNA level. A conclusion was drawn that the over expression of CenpB gene probably relates to malignant cell proliferation in breast gland. It has been testified by researchers that a few of CenpB homogenous proteins are co-operative, the loss of their genes resulting in chromosomes' separating abnormally and cell growth's slowing down. Having transfected HeLa (Tet-Off) cells with anti-sense Cenp in a previous experiment, we ever got a result that cellular duplicating time was prolonged for another 32.8 h, and together with the inhibition of centromere assembly, the mitotic index dropped sharply. In another research, we drew a conclusion that CenpG may be related to cancer, and its differential expressing probably relates to malignant cell proliferation. Combined with these researches, the results obtained from the current study are beneficial to further recognition of the mechanism of cancer.