Metallothionein (MT) is a kind of metal binding protein. As an important member in metallothionein family, MT-I/II regulates metabolism and detoxication of brain metal ion and scavenges free radicals. It is capable of anti-inflammatory response and anti-oxidative stress so as to protect the brain tissue. During the repair process of brain injury, the latest study showed that MT-I/II could stimulate brain anti-inflammatory factors, growth factors, neurotrophic factors and the expression of the receptor, and promote the extension of axon of neuron, which makes contribution to the regeneration of neuron and has important effect on the recovery of brain injury. Based on the findings, this article reviews the structure, expression, distribution, adjustion, function, mechanism in the repair of brain injury of MT-I/II and its application prospect in forensic medicine. It could provide a new approach for the design and manufacture of brain injury drugs as well as for age estimation of the brain injury.
Animals ; Astrocytes/metabolism* ; Brain/metabolism* ; Brain Injuries/pathology* ; Cytokines/metabolism* ; Forensic Medicine/methods* ; Gene Expression Regulation/drug effects* ; Humans ; Metallothionein/physiology* ; Neurons/metabolism* ; Neuroprotective Agents/pharmacology* ; Oxidative Stress/drug effects*

OBJECTIVE[corrected] To assess the effects of metallothionein on myocyte apoptosis and energy supply of isolated rabbit heart muscle during perfusion with ropivacaine..

METHODSSixty New Zealand white male rabbits were randomized into 3 equal groups. In group I, the rabbits received a intreaperitioneal injection of distilled water 24 h before isolation of the heart with perfusion by Langendoff model; in group II, distilled water was injected intreaperitioneally, and 24 h later the heart was isolated and perfused with Langendoff model and ropivacaine; in group III, 3.6% ZnSO(4) was injected intreaperitioneally and the isolated heart was perfused with Langendoff model and ropivacaine. The myocardial metallothionein content, myocyte apoptosis, and myocardial ATP, ADP and AMP content were detected.

RESULTSThe myocardial metallothionein content was significantly higher in group III than in the other two groups; the percent of myocyte apoptosis was the highest in group II, and was significantly higher in group III than in group I. The myocardial content of ATP was the highest in group I, and was significantly higher in group III than in group II.

CONCLUSIONMetallothionein can significantly inhibit myocyte apoptosis and alleviate energy supply disorder induced by ropivacaine.

Amides ; pharmacology ; Animals ; Apoptosis ; drug effects ; Energy Metabolism ; drug effects ; In Vitro Techniques ; Male ; Metallothionein ; pharmacology ; Myocardium ; cytology ; metabolism ; Myocytes, Cardiac ; cytology ; metabolism ; Perfusion ; Rabbits

OBJECTIVETo investigate anticancer effect and potential mechanism of tanshinone II(A) (Tan II(A)) on human nasopharyngeal carcinoma cell line CNE cells.

METHODAntiproliferative effect of Tan II(A) on CNE cells was evaluated by morphological examination, cell growth curves, colonial assay and MTT assay. Apoptosis detection was carried out using Hoechest 33258 and PI double-dyeing method. Intracellular Ca2+ concentration and mitochondria membrane potential were detected by fluorospectrophotometer. Bad and MT-1A transcript analysis in CNE cells was analyzed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR).

RESULTTan II(A) could inhibit CNE cells proliferation in dose- and time-dependent manner. 50% inhibiting concentration of Tan II(A) on CNE cells in 24, 48, 72 h was 45.7, 24.8, 3.3 mg x L(-2), respectively. Typical apoptotic morphology such as chromatin aggregation was observed in CNE cells with Tan II(A) treated for 24 h, and the apoptotic inducing effect was in a dose-dependent manner. After treated with Tan II(A), intracellular Ca2+ concentration of CNE cells was increased, mitochondria membrane potential of the cells was decreased, relative mRNA level of Bad and MT-1A was up-regulated.

CONCLUSIONTan II(A) had anticancer effect on CNE cells through apoptosis via calcineurin-dependent pathway and MT-1A downregulation.

Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Calcium ; metabolism ; Carcinoma ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Diterpenes, Abietane ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Membrane Potential, Mitochondrial ; drug effects ; Metallothionein ; genetics ; Nasopharyngeal Neoplasms ; genetics ; metabolism ; pathology ; Signal Transduction ; drug effects ; bcl-Associated Death Protein ; genetics

Badu Shengji San(BDSJS) is a traditional Chinese medicine (TCM) used for drawing out toxin, eliminating suppuration and promoting granulation. Toxic minerals such as arsenic and lead are the two most important components of BDSJS. Previous hypothesis indicated that according to the compatibility theory of TCM, the toxicity of the entire BDSJS was weaker than that of arsenic and lead, respectively. In the present study, SD rats with injured skin were treated with distilled water and different composition of BDSJS (complete formulations, compatible herbs, mineral medicine containing arsenic and lead, mineral medicine containing arsenic and mineral medicine containing lead) once a day for consecutive 2 weeks. Kidney coefficient and urinary beta-N-acetyl glucosidase (NAG) were used as the indicators of renal toxicity and the content of malondiadehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), glutathione (GSH) and metallothionein (MT) in the renal tissue were measured. Our data showed that kidney coefficient, the severity of renal pathological lesion and MT level in the kidney of the entire BDSJS group decreased significantly compared with arsenic and lead group. Additionally, the NAG content of the entire BDSJS group had the decreased trend. The kidney CuZn-SOD level of the entire BDSJS group had the increased trend, but the MDA, GSH-PX, GSH level had no obvious difference. Our results suggested that compatible herbs in BDSJS relieved renal injury induced by arsenic and lead, and the attenuation mechanism may be related to MT and CuZn-SOD, but not to MDA, GSH-PX and GSH directly.
Animals ; Arsenic ; toxicity ; Body Weight ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; toxicity ; Glutathione ; metabolism ; Glutathione Peroxidase ; metabolism ; Kidney ; drug effects ; metabolism ; pathology ; Lead ; toxicity ; Male ; Malondialdehyde ; metabolism ; Metallothionein ; metabolism ; Rats ; Rats, Sprague-Dawley ; Skin ; drug effects ; Superoxide Dismutase ; metabolism

OBJECTIVETo study the gene expression of metallothionein 1 (MT-1) isoforms in human peripheral blood lymphocytes (HPBLs).

METHODSThe expression of mRNA representing the seven active MT-1 genes was determined in HPBLs by quantitative RT-PCR before and after exposure to cadmium.

RESULTSBasal expressions of MT-1X, and MT-1A in HPBLs were similar to expression of housekeeping gene. In contrast, the basal gene expressions of MT-1H, 1F, 1E, and 1G were a little transcripts in human HPBLs. No signal was detected for MT-1B. There was a sex difference (P < 0.05). in basal gene expression of MT-1E. The levels of gene expression of MT-1A, 1E, 1F, 1G, 1H, and 1X increased, but the level of MT-1B did not increase after exposure to cadmium.

CONCLUSIONSGene expressions of MT-1G, MT-1H, MT-1F, and MT-1X in HPBLs can be used as a potential biomarker of cadmium exposure.

Adult ; Biomarkers ; metabolism ; Cadmium ; pharmacology ; Cells, Cultured ; DNA Primers ; Female ; Gene Expression Regulation ; drug effects ; Humans ; Lymphocytes ; metabolism ; Male ; Metallothionein ; genetics ; metabolism ; Protein Isoforms ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

People with upper body or visceral obesity have a much higher risk of morbidity and mortality from obesity-related metabolic disorders than those with lower body obesity. In an attempt to develop therapeutic strategies targeting visceral obesity, depot- specific differences in the expression of genes in omental and subcutaneous adipose tissues were investigated by DNA array technology, and their roles in adipocyte differentiation were further examined. We found that levels of metallothionein-II (MT-II) mRNA and protein expression were higher in omental than in subcutaneous adipose tissues. The study demonstrates that MT-II may play an important role in adipocyte differentiation of 3T3L1 preadipocytes, and that N-acetylcysteine (NAC) inhibits the adipocyte differentiation of 3T3L1 cells by repressing MT-II in a time- and dose-dependent manner. Furthermore, the intraperitoneal administration of NAC to rats and mice resulted in a reduction of body weights, and a marked reduction in visceral fat tissues. These results suggest that MT-II plays important roles in adipogenesis, and that NAC may be useful as an anti-obesity drug or supplement.
Viscera/drug effects/metabolism ; Time Factors ; Subcutaneous Fat/drug effects ; Rats, Sprague-Dawley ; Rats ; Middle Aged ; Mice, Inbred C57BL ; Mice ; Metallothionein/*genetics/metabolism/physiology ; Male ; Humans ; Female ; Down-Regulation/drug effects/genetics ; Dose-Response Relationship, Drug ; Cell Differentiation/drug effects ; Body Weight/drug effects ; Anti-Obesity Agents/*pharmacology ; Animals ; Aged ; Adipose Tissue/cytology/drug effects/metabolism ; Adipocytes/cytology/drug effects/metabolism ; Acetylcysteine/*pharmacology ; 3T3-L1 Cells

OBJECTIVETo investigate whether renal dysfunction induced by cadmium is related to plasma anti-metallothionein antibody (anti-MT Ab) in workers occupationally exposed to cadmium.

METHODSThe male workers in a smeltery were selected as the subjects for the exposure and effect assessment. The urine cadmium (UCd), the blood cadmium (BCd) and the occupational cadmium intake (TTCd) served as the exposure indexes while the urine beta(2) microglobulin (Ubeta(2)-MG), the N-acetyl-beta-D-glucosaminidase (UNAG) and the urine albumin concentration (UALB) served as the effect markers for the renal dysfunction caused by the cadmium. The titer of the plasma anti-metallothionein antibody was determined with the enzyme linked immunosorbent assay (ELISA).

RESULTSThe UCd (3.16 microg/g Cr), BCd (9.28 microg/L), Ubeta(2)-MG (81.17 microg/g Cr) and UALB (7.03 mg/g Cr) in the occupational cadmium exposure group were significantly higher than those in the control group and the Ubeta(2)-MG, UNAG and UALB as well as the occurrence rate of abnormality would be increased with the increase of the level of the occupational cadmium exposure. There was no significant difference in the titer of anti-MT Ab between the exposure group and the control group (P > 0.05). The titer of the anti-MT Ab would not be increased with the increase of the dosage of the exposure and had no significant correlation with BCd, UCd and TTCd (P > 0.05). The positive correlation were found between anti-MT Ab and UNAG as well as between anti-MT Ab and Ubeta(2)-MG in the exposure group with the correlation coefficient of 0.302 and 0.218 respectively. The workers with high level anti-MT Ab are more susceptible to cadmium nephrotoxicity than those with low anti-MT Ab with the odds ratio (OR) value of 4.200 and the 95% CI between 1.213 and 14.541 (P < 0.05).

CONCLUSIONThere is a dose-effect relationship between cadmium exposure and renal dysfunction in workers occupationally exposed to cadmium, but no correlation is found between cadmium exposure and plasma anti-MT Ab. The workers occupationally exposed to the cadmium with higher level of anti-MT Ab are easier to suffer from renal dysfunction caused by cadmium. Plasma anti-MT Ab could be used as a biomarker of susceptibility in the workers exposed to cadmium.

Acetylglucosaminidase ; urine ; Autoantibodies ; blood ; Biomarkers ; urine ; Cadmium ; metabolism ; pharmacology ; Dose-Response Relationship, Drug ; Humans ; Kidney ; drug effects ; immunology ; physiopathology ; Kidney Function Tests ; Male ; Metallothionein ; immunology ; Occupational Exposure ; beta 2-Microglobulin ; urine

OBJECTIVEIn order to explore the toxic effects of cadmium on functions of endocrine and exocrine of pancreas.

METHODS96 SD rats were administered with cadmium at different doses (0, 50, 100, 200 mg/L) by drinking water for 30 days, 60 days and 90 days. The contents of cadmium and zinc in the blood and pancreas, also the glucose level in blood and urine, the levels of insulin and the activity of amylase were determined. The gene expression of metallothionein (MT), insulin and pancreatic amylase were also measured.

RESULTSThe results showed that the contents of cadmium in the serum and pancreas were higher than that of the control groups (P < 0.05). The contents of zinc in serum were decreased in the groups of 100 and 200 mg/L cadmium at the 90-day. As well as increased zinc in pancreas. The gene expression of insulin was not different compared with those of the control group except the middle-dose group at the 60-day. And the expression of amylase were higher in the groups of 100 and 200 mg/L cadmium at the 60-day and the 90-day. The expression of MT-1 and -2 were higher in the pancreas after cadmium administration.

CONCLUSIONIt is suggested that cadmium could be accumulated in the pancreas and caused the change of the zinc levels. Then it resulted in the change of the expression of gene and protein, and influence of the functions of both endocrine and exocrine in pancreas.

Amylases ; metabolism ; Animals ; Cadmium ; toxicity ; Female ; Insulin ; metabolism ; Male ; Metallothionein ; metabolism ; Pancreas ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Zinc ; blood

Homocysteine ; pharmacology ; Human Umbilical Vein Endothelial Cells ; drug effects ; metabolism ; Humans ; Lipid Peroxidation ; drug effects ; Metallothionein ; pharmacology

OBJECTIVETo study the possible intervention of isoflavones in cytotoxicity induced by cadmium in vascular endothelial cells.

METHODSAn ECV 304 cell line derived from human umbilical vein endothelial cells was adopted. Genistein/daidzein was added prior to or simultaneously with CdCl2, cell viability was determined by MTT assay, and metallothionein mRNA expression was monitored by RT-PCR method.

RESULTSCell viability was higher in isoflavone and CdCl2 co-treated groups than that in CdCl2 treated group, with CdCl2 concentration at 10, 20, 40, and 80 micromol/L, respectively. However this increase was not observed in the group treated with CdCl2 at a concentration of 60 micromol/L. Isoflavones (10(-10) mol/L to 10(-5) mol/L) were added 24 h before cells were challenged with 80 micromol/L CdCl2 for 24 h or simultaneously with 80 micromol/L CdCl2. Genistein increased cell viability only at 10(-5) mol/L, while daidzein caused a dose-dependent increase from 10(-10) mol/L to 10(-5) mol/L in co-treatment with CdCl2. In pre-treatment, genistein (10(-7) to 10(-5) mol/L) increased cell viability whereas only 10(-5) mol/L of daidzein exerted protection. Apparent protection could be found when the cells were pre-treated with 10(-5) mol/L isoflavones for over 12 h, whereas 24 h incubation was required in such a co-treatment, with the exception of daidzein that had a significant protection in only 3 h. Isoflavones (10(-6) mol/L) incubated for 3 h to 24 h, increased MT IIA and MT IF mRNA expression, but the induction could not last for more than 24 h. Co-treatment with isoflavones could induce an additional induction of MT IIA mRNA expression in cells exposed to cadmium. However, the additional induction of MT IIA and MT IF mRNA was not seen when pre-treatment was carried out with isoflavones, with the exception of an increase in MT IIA mRNA expression in the daidzein pre-treated group.

CONCLUSIONGenistein/daidzein could reverse the cytotoxicity of cadmium either in pre-treatment or in co-treatment. The protection is the strongest in 10(-5) mol/L of isoflavones with a dose-dependent pattern. There are differences between genistein and daidzein in their protective effects. Whether the protection of isoflavones is related to their capacity of inducing MT mRNA expression remains to be elucidated.

Cadmium ; toxicity ; Cell Line ; Cell Survival ; drug effects ; Endothelial Cells ; drug effects ; metabolism ; Genistein ; pharmacology ; Humans ; Isoflavones ; pharmacology ; Metallothionein ; genetics ; metabolism ; Protective Agents ; pharmacology ; RNA, Messenger ; metabolism