Font Size: a A A

Exploring A Novel Metallothionein Induced By Selenium

Posted on:2004-02-04Degree:MasterType:Thesis
Country:ChinaCandidate:Z YongFull Text:PDF
GTID:2144360092496822Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Metallothionein (MT) is a group of cysteine-rich, low molecular weight, metal-binding intracellular protein which are widely distributed in nature. It has been proved that MT is closely correlative with essential metal metabolism, heavy metal detoxification, anti-radiation, anti-oxidation, cleaning free radical, apoptosis and proliferation of tumor cells and energy metabolism et al. A noticeable behavior of MT is its induction and the synthesis of MT can be increased by heavy metal toxicity and hormone stimulate, which can bind with many metal elements. It is reported clearly at present that those metal elements, which can induce MT, are involved with Cd, Hg, Zn, Cu, Ag, Au, Pd, Ni, Cr, Sn, Co, Fe and Bi. Cd and Zn are been considered better inducers of MT. Because Cd is a harmful heavy metal element, researchers pay close attention to Zn in their studies. At present Zn is considered as the least toxic MT inducer. However, it is reported the mutagenic action of Zn at very low concentrations recently. Therefore, the safety of zinc supplements should be reconsidered.The aim of this study is to prove (1) the inductive effect of Se on MT by using more specific and sensitive methods; (2) the presence of Se-MT for exploring a more safe and active novel MT; (3) evaluating the biological effect of Se-MT.In the first part, we screened different substances containing Zinc, Cadmium andSelenium elements by using Hg-Chelex and ELISA. The results showed that 1. To our surprise the non-metal element, selenium especially organic selenium (Selenium malt, Se-malt) has extremely strong MT inducing effects compared with metal elements Cd and Zn; (2) The ability of organic selenium to induce MT was greater than Zinc and Cadmium that were thought as the most active elements to induce MT at present. The ability of organic selenium to induce MT was 1-2 folds higher than that of Zinc. Aboveresults present the existence of a. novel Se-MT and the possibility for exploring the biology of Se-MT.In the second part, Se-MT was isolated, purified, identified and compared with Zn-MT simultaneously. The results showed that the content of Se element in the Se-MT was 2.5 folds higher than that of Zn-MT, on the contrary the content of sulfur element in Se-MT was 2 folds lower then Zn-MT, C, H, N contents in MT were no significant differences in both groups. In terms of chemical property, the element of selenium is very similar to sulfur because they are in the same group in the periodic table. The above results illustrated that the Se could replace S from SH-sulfhydryl to SeH-selenihydryl in cysteine, which presents the existence of a novel Se-MT.In the third part, the biological effects of Se-MT were evaluated by an animal model of liver fibrosis induced by alcohol, based upon the high expression of MT in liver. The prevent effects against rats liver fibrosis were determined by pathologic observation and biochemical methods (SOD and MDA), as well as liver tissue protein fingerprinting determined by surface-enhanced laser desorption/ionization -time of flight mass spectrometry (SELDI). Results of pathology showed that the histological structure in Se treated group was similar with control; otherwise, the injury group expressed liver fibrosis pathologic changes. Biochemical examine also indicated that there was no significant different in MDA value between Se treated group (0.95 ± 0. 064 P<0.05) and control (0.55±0.133 P<0.05), but the injury group (1.52±0.081 P<0.05). The protein fingerprinting of liver tissue lyses determined by SELDI-TOF-MASS expressed that the ratio of peak current intensity in 5130 Da/5142 Da was upside down in the injury group, but not in the control and Se treated group.Above results verified that the MT induced by organic selenium (Se-malt) had remarkable protective effects against alcoholic liver fibrosis. This finding provided a good reference for the further study in the preventive effect to against hepatitis B viruscaused liver fibrosis by Se-malt. Meanwhile, in this study the protein fingerp...
Keywords/Search Tags:Metallothionein, Selenium, Liver fibrosis, Protein fingerprinting
PDF Full Text Request
Related items