RESUMO
Siderophore-mimicking macrocyclic peptoids were synthesized. Peptoid 3 with intramolecular hydrogen bonds showed an optimally arranged primary coordination sphere leading to a stable catecholate-iron complex. The tris(catecholato) structure of 3-Fe(iii) was determined with UV-vis, fluorescence, and EPR spectroscopies and DFT calculations. The iron binding affinity was comparable to that of deferoxamine, with enhanced stability upon air exposure.
Assuntos
Catecóis/química , Quelantes/química , Compostos Férricos/química , Peptoides/síntese química , Desferroxamina/química , Teoria da Densidade Funcional , Ligantes , Estrutura Molecular , Peptoides/químicaRESUMO
Aging study requires aging markers to measure the degree of aging process. The aging markers such as senescence associated-ß-galactosidase (SA-ß-gal), lipofuscin, telomere, p53 and p16 have been known in aging study until now. Therefore, we investigated the role of genes and proteins related to aging in young, senescent and H2O2-induced old cells to develop a novel aging marker involved in aging mechanism. After cellular aging was compared in young, senescent and H2O2-induced old cells using SA-ß-galactosidase staining assay, the expression level of genes and proteins in senescent and H2O2-induced old cells were compared and analyzed with those of young cells using RT-PCR, western blot and immunofluorescence staining. First of all, the senescent cells and the cells aged by H2O2 showed higher level of SA-ß-galactosidase staining than young cells. In particular, the expression level of IGFBP-3 was decreased in senescent and H2O2-induced old cells compared with young cells. Moreover, the senescent and H2O2-induced old cells showed higher expression levels of p-PI3K, Akt-1, p-mTOR, p-FoxO1 and FoxO1 than young cells. Furthermore, the expression levels of p300, Ac-p53, p53, p-p21 and p16 were significantly increased in senescent and H2O2-induced cells compared to young cells. However, the expression level of SIRT-1 was decreased in senescent and H2O2-induced old cells compared to young cells. In conclusion, IGFBP-3 up-regulates PI3K/Akt/mTOR signaling pathway and down-regulates autophagy during cell aging. These results suggest that IGFBP-3 could play a key role in aging study as an important aging marker.
Assuntos
Senescência Celular/fisiologia , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina , Biomarcadores/metabolismo , Linhagem Celular , Proteína Forkhead Box O1/metabolismo , Humanos , Peróxido de Hidrogênio , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
Chitooligosaccharides (COS) have been reported to show a variety of biological efficacies such as anti-bacterial activity, anti-tumor activity and immune activity. The purpose of this study is to investigate the inhibitory effect of aminoethyl-chitooligosaccharides (AE-COS) synthesized from COS that were substituted hydroxyl groups with aminoethyl group at C-6 position on cell invasion of human fibrosarcoma cells. First of all, the effect of AE-COS on cell viability was observed using MTT assay. The cytotoxicity of AE-COS was increased in a dose dependent manner. The inhibitory effects of AE-COS on the activity and expression level of MMP-2 and MMP-9 related to invasion of cancer cells were examined using gelatin zymography and western blot. It was found that AE-COS above 20µg/ml showed the inhibitory effect on the activity and expression of MMP-9. Furthermore, AE-COS at 20µg/ml reduced the expression level of p50, a part of NF-κB, compared with phorbol-12- myristate-13- acetate (PMA) group. The available data let us hypothesize that AE-COS could provide chemoprevention as an inhibitor against cell invasion associated with metastasis.