A Distinct Gene Module for Dysfunction Uncoupled from Activation in Tumor-Infiltrating T Cells.

Reversing the dysfunctional T cell state that arises in cancer and chronic viral infections is the focus of therapeutic interventions; however, current therapies are effective in only some patients and some tumor types. To gain a deeper molecular understanding of the dysfunctional T cell state, we analyzed population and single-cell RNA profiles of CD8(+) tumor-infiltrating lymphocytes (TILs) and used genetic perturbations to identify a distinct gene module for T cell dysfunction that can be uncoupled from T cell activation. This distinct dysfunction module is downstream of intracellular metallothioneins that regulate zinc metabolism and can be identified at single-cell resolution. We further identify Gata-3, a zinc-finger transcription factor in the dysfunctional module, as a regulator of dysfunction, and we use CRISPR-Cas9 genome editing to show that it drives a dysfunctional phenotype in CD8(+) TILs. Our results open novel avenues for targeting dysfunctional T cell states while leaving activation programs intact.

Pleural CD14+ monocytes/macrophages of healthy adolescents show a high expression of metallothionein family genes.

Nowadays laparoscopic interventions enable the collection of resident macrophage populations out of the human cavities. We employed this technique to isolate pleural monocytes/macrophages from healthy young adults who underwent a correction of pectus excavatum. High quality CD14+ monocytes/macrophages (plMo/Mφ) were used for RNA-sequencing (RNA-seq) in comparison with human monocyte-derived macrophages (MDM) natural (MDM-0) or IL-4-polarized (MDM-IL4). Transcriptome analysis revealed 7166 and 7076 differentially expressed genes (DEGs) in plMo/Mφ relative to natural MDM-0 and polarized MDM-IL4, respectively. The gene set enrichment analysis, which was used to compare RNA-seq data from plMo/Mφ with single-cell (scRNA-seq) data online from human bronchial lavage macrophages, showed that plMo/Mφs are characterized by a high expression of genes belonging to the metallothionein (MT) family, and that the expression of these genes is significantly higher in plMo/Mφ than in MDM-0 or MDM-IL4. Our results provide additional insights on high MTs-expressing macrophage subsets, which seem to be present not only in bronchial lavage of healthy adults or in pleural exudates of lung cancer patients but also in pleural fluid of healthy young adults. Macrophage subsets expressing high MTs may have specific roles in lung defense, repair, and homeostasis, and require further investigations.

Inoculation of heavy metal resistant bacteria alleviated heavy metal-induced oxidative stress biomarkers in spinach (Spinacia oleracea L.).

Most vegetable crops are severely affected by the uptake of heavy metals from the soil. Heavy metals in vegetable bodies generate reactive oxygen species (ROS) that unbalance the antioxidant defense system. This study was initiated to determine the physiological and biochemical characteristics of spinach plants grown on soil contaminated with heavy metals and responding to Bacillus cereus and Bacillus aerius were isolated from soil contaminated with heavy metals. Heavy metal contamination led to a significant reduction in seed germination, seedling biomass, protein, and total nitrogen content of spinach plants grown in contaminated soils compared to control soils. In contrast, a significant increase in the content of metallothioneins and antioxidant enzymes was observed. Plants inoculated with B. cereus and B. aerius significantly reduced the oxidative stress induced by heavy metals by improving seed germination (%), seedling growth, nitrogen, and protein content. The content of metallothioneins and the activities of antioxidant enzymes were reduced in spinach plants grown from seeds inoculated with bacterial strains. In addition, plants inoculated with, B. cereus and B. aerius showed greater stomata opening than plants grown on soil contaminated with heavy metals, whose stomata were almost closed. These results suggested that both bacterial strains enhanced plant growth by reducing oxidative stress caused by metals.

Immunogenetic and Environmental Factors in Age-Related Macular Disease.

Age-related macular degeneration (AMD) is a chronic disease, which often develops in older people, but this is not the rule. AMD pathogenesis changes include the anatomical and functional complex. As a result of damage, it occurs, in the retina and macula, among other areas. These changes may lead to partial or total loss of vision. This disease can occur in two clinical forms, i.e., dry (progression is slowly and gradually) and exudative (wet, progression is acute and severe), which usually started as dry form. A coexistence of both forms is possible. AMD etiology is not fully understood. Extensive genetic studies have shown that this disease is multifactorial and that genetic determinants, along with environmental and metabolic-functional factors, are important risk factors. This article reviews the impact of heavy metals, macro- and microelements, and genetic factors on the development of AMD. We present the current state of knowledge about the influence of environmental factors and genetic determinants on the progression of AMD in the confrontation with our own research conducted on the Polish population from Kuyavian-Pomeranian and Lubusz Regions. Our research is concentrated on showing how polluted environments of large agglomerations affects the development of AMD. In addition to confirming heavy metal accumulation, the growth of risk of acute phase factors and polymorphism in the genetic material in AMD development, it will also help in the detection of new markers of this disease. This will lead to a better understanding of the etiology of AMD and will help to establish prevention and early treatment.

Identification of critical genes associated with lead exposure based on in silico analysis.

High blood levels of lead have been shown to relate to its toxicity, and its early detection in occupational workers is important to take necessary measures. The genes associated with lead toxicity were identified by in silico analysis of expression profile (GEO-GSE37567) based on lead exposure of peripheral blood mononuclear cells maintained in culture. The GEO2R tool was used to identify differentially expressed genes (DEGs) among three groups: control versus day-1 treatment, control versus day-2 treatment, and control versus day-1 treatment versus day-2 treatment, and their enrichment analysis was performed to categorize them for molecular function, biological process, cellular component, and KEGG pathways. The protein-protein interaction (PPI) network of DEGs was constructed using a STRING tool and hub genes were identified by using the CytoHubba plugin of Cytoscape. Top 250 DEGs were screened in the first and second groups and 211 DEGs were in the third group. Fifteen critical genes viz. MT1G, ASPH, MT1F, TMEM158, CDK5RAP2, BRCA2, MT1E, EDNRB, MT1H, KITLG, MT1X, MT2A, ARRDC4, MT1M, and MT1HL1 were selected for functional enrichment and pathway analysis. The DEGs were primarily enriched in metal ion binding, metal absorption, and cellular response to metal ions. The significantly enriched KEGG pathways included mineral absorption, melanogenesis, and cancer signaling pathways. PPI network analysis revealed that seven genes of the MT family exhibited good connectedness and served as a marker of lead induced toxicity. Our study suggests that MT1E, MT1H, MT1G, MT1X, MT1F, MT1M, and MT2A of the metallothioneins gene family may act as potential biomarkers to monitor lead exposure.

Modularity in Protein Evolution: Modular Organization and De Novo Domain Evolution in Mollusk Metallothioneins.

Metallothioneins (MTs) are proteins devoted to the control of metal homeostasis and detoxification, and therefore, MTs have been crucial for the adaptation of the living beings to variable situations of metal bioavailability. The evolution of MTs is, however, not yet fully understood, and to provide new insights into it, we have investigated the MTs in the diverse classes of Mollusks. We have shown that most molluskan MTs are bimodular proteins that combine six domains-α, ß1, ß2, ß3, γ, and δ-in a lineage-specific manner. We have functionally characterized the Neritimorpha ß3ß1 and the Patellogastropoda γß1 MTs, demonstrating the metal-binding capacity of the new γ domain. Our results have revealed a modular organization of mollusk MT, whose evolution has been impacted by duplication, loss, and de novo emergence of domains. MTs represent a paradigmatic example of modular evolution probably driven by the structural and functional requirements of metal binding.

Immunolocalization of zinc transporters and metallothioneins reveals links to microvascular morphology and functions.

Zinc homeostasis is vital to immune and other organ system functions, yet over a quarter of the world's population is zinc deficient. Abnormal zinc transport or storage protein expression has been linked to diseases, such as cancer and chronic obstructive pulmonary disorder. Although recent studies indicate a role for zinc regulation in vascular functions and diseases, detailed knowledge of the mechanisms involved remains unknown. This study aimed to assess protein expression and localization of zinc transporters of the SLC39A/ZIP family (ZIPs) and metallothioneins (MTs) in human subcutaneous microvessels and to relate them to morphological features and expression of function-related molecules in the microvasculature. Microvessels in paraffin biopsies of subcutaneous adipose tissues from 14 patients undergoing hernia reconstruction surgery were analysed for 9 ZIPs and 3 MT proteins by MQCM (multifluorescence quantitative confocal microscopy). Zinc regulation proteins detected in human microvasculature included ZIP1, ZIP2, ZIP8, ZIP10, ZIP12, ZIP14 and MT1-3, which showed differential localization among endothelial and smooth muscle cells. ZIP1, ZIP2, ZIP12 and MT3 showed significantly (p < 0.05) increased immunoreactivities, in association with increased microvascular muscularization, and upregulated ET-1, α-SMA and the active form of p38 MAPK (Thr180/Tyr182 phosphorylated, p38 MAPK-P). These findings support roles of the zinc regulation system in microvascular physiology and diseases.

Transcriptomic and functional analysis of Aß1-42 oligomer-stimulated human monocyte-derived microglia-like cells.

Dysregulation of microglial function contributes to Alzheimer's disease (AD) pathogenesis. Several genetic and transcriptome studies have revealed microglia specific genetic risk factors, and changes in microglia expression profiles in AD pathogenesis, viz. the human-Alzheimer's microglia/myeloid (HAM) profile in AD patients and the disease-associated microglia profile (DAM) in AD mouse models. The transcriptional changes involve genes in immune and inflammatory pathways, and in pathways associated with Aß clearance. Aß oligomers have been suggested to be the initial trigger of microglia activation in AD. To study the direct response to Aß oligomers exposure, we assessed changes in gene expression in an in vitro model for microglia, the human monocyte-derived microglial-like (MDMi) cells. We confirmed the initiation of an inflammatory profile following LPS stimulation, based on increased expression of IL1B, IL6, and TNFα. In contrast, the Aß1-42 oligomers did not induce an inflammatory profile or a classical HAM profile. Interestingly, we observed a specific increase in the expression of metallothioneins in the Aß1-42 oligomer treated MDMi cells. Metallothioneins are involved in metal ion regulation, protection against reactive oxygen species, and have anti-inflammatory properties. In conclusion, our data suggests that exposure to Aß1-42 oligomers may initially trigger a protective response in vitro.

Bioinformatic prediction of putative metallothioneins in non-ciliate protists.

Intracellular ligands that bind heavy metals (HMs) and thereby minimize their detrimental effects to cellular metabolism are attracting great interest for a number of applications including bioremediation and development of HM-biosensors. Metallothioneins (MTs) are short, cysteine-rich, genetically encoded proteins involved in intracellular metal-binding and play a key role in detoxification of HMs. We searched approximately 700 genomes and transcriptomes of non-ciliate protists for novel putative MTs by similarity and structural analyses and found 21 unique proteins playing a potential role as MTs. Most putative MTs derive from heterokonts and dinoflagellates and share common features such as (i) a putative metal-binding domain in proximity of the N-terminus, (ii) two putative MT-specific domains near the C-terminus and (iii) one to three CTCGXXCXCGXXCXCXXC patterns. Although the biological function of these proteins has not been experimentally proven, knowledge of their genetic sequences adds useful information on proteins that are potentially involved in HM-binding and can contribute to the design of future biomolecular assays on HM-microbe interactions and MT-based biosensors.

Does roundup affect zinc functions in a bivalve mollusk in ex vivo exposure?

Roundup (Rn), a glyphosate-based formulation, is one of the most commonly used herbicides in the world. It affects non-targeted organisms in several ways, including adhesive activity towards metal ions. Zinc (Zn) plays a crucial role in a number of biochemical processes. In this study, we aim to elucidate the direct impact of Rn on Zn accumulation and Zn-dependent activities in the ex vivo system. To this end, we exposed the samples of the digestive gland of a bivalve mollusk Unio tumidus to 3 µM of Rn (calculated as 3 µM of glyphosate), Zn, Zn chelator (N,N,N',N'-Tetrakis(2-pyridylmethyl)ethylenediamine) (TPEN, Tp), and their combinations ZnTp and ZnRn for 17 h. We determined the levels of Zn in the tissue (Zn t) and metallothioneins (Zn-MT), metallothioneins (MTSH), and glutathione (GSH & GSSG), total antioxidant capacity (TAC), lysosomal membrane integrity, and caspase-3 activity. Our study demonstrated that Rn and Tp had different effects on the accumulation and functionality of Zn. Rn did not affect the accumulation of Zn (Zn t, Zn-MT) in the Zn- and ZnRn-groups. On the contrary, Tp produced effects antagonistic to Zn on caspase-3 activity, lysosomal stability, and MTSH concentration. Rn caused particular pro-oxidative effect that decreased GSH level (Rn- and ZnRn-groups) and lysosomal stability (Rn-group). The shared affected index was the GSH/GSSG ratio, which decreased by 2-8 times in each exposure. As the first experience with the application of Tp to indicate Zn activity in mollusks, the study concluded that the ex vivo approach could be useful in the study of numeral aquatic pollutants.

Metallothionein Expression as a Physiological Response against Metal Toxicity in the Striped Rockcod Trematomus hansoni.

Metal bioaccumulation and metallothionein (MT) expression were investigated in the gills and liver of the red-blooded Antarctic teleost Trematomus hansoni to evaluate the possibility for this species to face, with adequate physiological responses, an increase of copper and cadmium concentrations in its tissues. Specimens of this Antarctic fish were collected from Terra Nova Bay (Ross Sea) and used for a metal exposure experiment in controlled laboratory conditions. The two treatments led to a significant accumulation of both metals and increased gene transcription only for the MT-1. The biosynthesis of MTs was verified especially in specimens exposed to Cd, but most of these proteins were soon oxidized, probably because they were involved in cell protection against oxidative stress risk by scavenging reactive oxygen species. The obtained data highlighted the phenotypic plasticity of T. hansoni, a species that evolved in an environment characterized by naturally high concentrations of Cu and Cd, and maybe the possibility for the Antarctic fish to face the challenges of a world that is becoming more toxic every day.

High pH Alleviated Sweet Orange (Citrus sinensis) Copper Toxicity by Enhancing the Capacity to Maintain a Balance between Formation and Removal of Reactive Oxygen Species and Methylglyoxal in Leaves and Roots.

The contribution of reactive oxygen species (ROS) and methylglyoxal (MG) formation and removal in high-pH-mediated alleviation of plant copper (Cu)-toxicity remains to be elucidated. Seedlings of sweet orange (Citrus sinensis) were treated with 0.5 (non-Cu-toxicity) or 300 (Cu-toxicity) µM CuCl2 × pH 4.8, 4.0, or 3.0 for 17 weeks. Thereafter, superoxide anion production rate; H2O2 production rate; the concentrations of MG, malondialdehyde (MDA), and antioxidant metabolites (reduced glutathione, ascorbate, phytochelatins, metallothioneins, total non-protein thiols); and the activities of enzymes (antioxidant enzymes, glyoxalases, and sulfur metabolism-related enzymes) in leaves and roots were determined. High pH mitigated oxidative damage in Cu-toxic leaves and roots, thereby conferring sweet orange Cu tolerance. The alleviation of oxidative damage involved enhanced ability to maintain the balance between ROS and MG formation and removal through the downregulation of ROS and MG formation and the coordinated actions of ROS and MG detoxification systems. Low pH (pH 3.0) impaired the balance between ROS and MG formation and removal, thereby causing oxidative damage in Cu-toxic leaves and roots but not in non-Cu-toxic ones. Cu toxicity and low pH had obvious synergistic impacts on ROS and MG generation and removal in leaves and roots. Additionally, 21 (4) parameters in leaves were positively (negatively) related to the corresponding root parameters, implying that there were some similarities and differences in the responses of ROS and MG metabolisms to Cu-pH interactions between leaves and roots.

Environmental biomonitoring by snails.

Background: Bio-indicator systems are vital in terms of monitoring of pollutants around the world. The impact of environmental change can be monitored by employing the responsive behaviour of snails. Heavy metal and organic pollutants affects snail reproduction, mortality, and normal metabolic activities. Various changes like a discontinuity in food intake, growth rate, twitching, and quenching of tentacles, are the biomarkers of the snails for biomonitoring. Different snails can bio-monitor eco-toxicological urban pollution, oil pollutant, terrestrial pollution, pesticide pollutants, mercury contamination, ammonia, chlorinated paraffin in soil, ethanol in water, ocean acidification pollutions. These animals can also make bio-sense about diverse environment spheres, which include the biosphere, lithosphere, anthroposphere, cryosphere, and hydrosphere.Methods: We examined the scientific literature and related articles listed in Pub-med, Google Scholar reporting on biomonitoring potential and biomarkers expression of various snail species and consequently explore the value of snails in the respective field by discussing various outcomes of a number of studies on the pollution biomonitoring and biosensing capabilities.Results: Several terrestrial, freshwater and sea snail species are characterized by the high sense of biomonitoring and biosensing potential. Various biomarkers such as expression of heat shock proteins and metallothioneins in the body are found to be the essential in-vivo biomarkers for pollution biomonitoring.Conclusion: It is observed that snails offer an environment friendly approach for the environmental bio monitoring by expressing their numerous physiological, biochemical, genetical and histological biomarkers in their body. Thus, it proved to be a critical bio monitoring tool and early warning indicators.

Metallothionein isoforms as double agents - Their roles in carcinogenesis, cancer progression and chemoresistance.

Metallothioneins (MTs) are small cysteine-rich intracellular proteins with four major isoforms identified in mammals, designated MT-1 through MT-4. The best known biological functions of MTs are their ability to bind and sequester metal ions as well as their active role in redox homeostasis. Despite these protective roles, numerous studies have demonstrated that changes in MT expression could be associated with the process of carcinogenesis and participation in cell differentiation, proliferation, migration, and angiogenesis. Hence, MTs have the role of double agents, i.e., working with and against cancer. In view of their rich biochemical properties, it is not surprising that MTs participate in the emergence of chemoresistance in tumor cells. Many studies have demonstrated that MT overexpression is involved in the acquisition of resistance to anticancer drugs including cisplatin, anthracyclines, tyrosine kinase inhibitors and mitomycin. The evidence is gradually increasing for a cellular switch in MT functions, showing that they indeed have two faces: protector and saboteur. Initially, MTs display anti-oncogenic and protective roles; however, once the oncogenic process was launched, MTs are utilized by cancer cells for progression, survival, and contribution to chemoresistance. The duality of MTs can serve as a potential prognostic/diagnostic biomarker and can therefore pave the way towards the development of new cancer treatment strategies. Herein, we review and discuss MTs as tumor disease markers and describe their role in chemoresistance to distinct anticancer drugs.

Bacterial adaptive strategies to cope with metal toxicity in the contaminated environment - A review.

Heavy metal contamination poses a serious environmental hazard, globally necessitating intricate attention. Heavy metals can cause deleterious health hazards to humans and other living organisms even at low concentrations. Environmental biotechnologists and eco-toxicologists have rigorously assessed a plethora of bioremediation mechanisms that can hamper the toxic outcomes and the molecular basis for rejuvenating the hazardous impacts, optimistically. Environmental impact assessment and restoration of native and positive scenario has compelled biological management in ensuring safety replenishment in polluted realms often hindered by heavy metal toxicity. Copious treatment modalities have been corroborated to mitigate the detrimental effects to remove heavy metals from polluted sites. In particular, Biological-based treatment methods are of great attention in the metal removal sector due to their high efficiency at low metal concentrations, ecofriendly nature, and cost-effectiveness. Due to rapid multiplication and growth rates, bacteria having metal resistance are advocated for metal removal applications. Evolutionary implications of coping with heavy metals toxicity have redressed bacterial adaptive/resistance strategies related to physiological and cross-protective mechanisms. Ample reviews have been reported for the bacterial adaptive strategies to cope with heavy metal toxicity. Nevertheless, a holistic review summarizing the redox reactions that address the cross-reactivity mechanisms between metallothionein synthesis, extracellular polysaccharides production, siderophore production, and efflux systems of metal resistant bacteria are scarce. Molecular dissection of how bacteria adapt themselves to metal toxicity can augment novel and innovative technologies for efficient detoxification, removal, and combat the restorative difficulties for stress alleviations. The present comprehensive compilation addresses the identification of newer methodologies, summarizing the prevailing strategies of adaptive/resistance mechanisms in bacterial bioremediation. Further pitfalls and respective future directions are enumerated in invigorating effective bioremediation technologies including overexpression studies and delivery systems. The analysis will aid in abridging the gap for limitations in heavy metal removal strategies and necessary cross-talk in elucidating the complex cascade of events in better bioremediation protocols.

Gold and silver nanoparticles effects to the earthworm Eisenia fetida - the importance of tissue over soil concentrations.

To address and to compare the respective impact of gold and silver nanoparticles (Au and Ag NPs) in soil invertebrate, the earthworm Eisenia fetida was exposed to soil containing 2, 10, and 50 mg/kg of Au and Ag in both nanoparticulate and ionic forms for 10 days. Both metal NPs were 2-15 times less bioavailable than their ionic forms, and displayed similar transfer coefficients from soil to earthworm tissues. Both metal NPs triggered the onset of an oxidative stress as illustrated by increased glutathione S-transferase levels, decreased catalase levels, and increased malondialdehyde concentrations. Protein carbonylation distinguished the nanoparticular from the ionic forms as its increase was observed only after exposure to the highest concentration of both metal NPs. Au and Ag NPs triggered DNA modifications even at the lowest concentration, and both repressed the expression of genes involved in the general defense and stress response at high concentrations as did their ionic counterparts. Despite the fact that both metal NPs were less bioavailable than their ionic forms, at equivalent concentrations accumulated within earthworms tissues they exerted equal or higher toxic potential than their ionic counterparts.Capsule: At equivalent concentrations accumulated within earthworm tissues Au and Ag NPs exert equal or higher toxic potential than their ionic forms.

Metal-Specificity Divergence between Metallothioneins of Nerita peloronta (Neritimorpha, Gastropoda) Sets the Starting Point for a Novel Chemical MT Classification Proposal.

Metallothioneins' (MTs) biological function has been a matter of debate since their discovery. The importance to categorize these cysteine-rich proteins with high coordinating capacity into a specific group led to numerous classification proposals. We proposed a classification based on their metal-binding abilities, gradually sorting them from those with high selectivity towards Zn/Cd to those that are Cu-specific. However, the study of the NpeMT1 and NpeMT2isoforms of Nerita peloronta, has put a new perspective on this classification. N. peloronta has been chosen as a representative mollusk to elucidate the metal-binding abilities of Neritimorpha MTs, an order without any MTs characterized recently. Both isoforms have been recombinantly synthesized in cultures supplemented with ZnII, CdII, or CuII, and the purified metal-MT complexes have been thoroughly characterized by spectroscopic and spectrometric methods, leading to results that confirmed that Neritimorpha share Cd-selective MTs with Caenogastropoda and Heterobranchia, solving a so far unresolved question. NpeMTs show high coordinating preferences towards divalent metal ions, although one of them (NpeMT1) shares features with the so-called genuine Zn-thioneins, while the other (NpeMT2) exhibits a higher preference for Cd. The dissimilarities between the two isoforms let a window open to a new proposal of chemical MT classification.

The Impact of Metal-Rich Sediments Derived from Mining on Freshwater Stream Life.

Metal-rich sediments have the potential to impair life in freshwater streams and rivers and, thereby, to inhibit recovery of ecological conditions after any remediation of mine water discharges. Sediments remain metal-rich over long time periods and have long-term potential ecotoxicological interactions with local biota, unless the sediments themselves are physically removed or replaced by less metal-rich sediment. Laboratory-derived environmental quality standards are difficult to apply to the field situation, as many complicating factors exist in the real world. Therefore, there is a strong case to consider other, field-relevant, measures of toxic effects as alternatives to laboratory-derived standards and to seek better biological tools to detect, diagnose and ideally predict community-level ecotoxicological impairment. Hence, this review concentrated on field measures of toxic effects of metal-rich sediment in freshwater streams, with less emphasis on laboratory-based toxicity testing approaches. To this end, this review provides an overview of the impact of metal-rich sediments on freshwater stream life, focusing on biological impacts linked to metal contamination.

Constitutive overexpression of rice metallothionein-like gene OsMT-3a enhances growth and tolerance of Arabidopsis plants to a combination of various abiotic stresses.

Metallothioneins (MT) are primarily involved in metal chelation. Recent studies have shown that MT proteins are also involved in the responses of plants to various environmental stresses. The rice metallothionein-like gene OsMT-3a is upregulated by salinity and various abiotic stressors. A DNA construct containing the complete OsMT-3a coding sequence cloned downstream to the CaMV35S promoter was transformed into Arabidopsis and homozygous single-copy transgenic lines were produced. Compared to wild-type plants, transgenic plants showed substantially increased salinity tolerance (NaCl), drought tolerance (PEG), and heavy metal tolerance (CdCl2) as individual stresses, as well as different combinations of these stresses. Relevantly, under unstressed control conditions, vegetative growth of transgenic plants was also improved. The shoot Na+ concentration and hydrogen peroxide in transgenic plants were lower than those in wild-type plants. OsMT-3a-overexpressing Arabidopsis lines accumulated higher levels of Cd2+ in both shoots and roots following CdCl2 treatment. In the transgenic MT-3a lines, increased activity of two major antioxidant enzymes, catalase and ascorbate peroxidase, was observed. Thus, rice OsMT-3a is a valuable target gene for plant genetic improvement against multiple abiotic stresses.

Polymorphisms in MMP-1, MMP-2, MMP-7, MMP-13 and MT2A do not contribute to breast, lung and colon cancer risk in polish population.

BACKGROUND: Matrix metalloproteinases (MMPs) and metallothioneins (MTs) are Zinc-related proteins which are involved in processes crucial for carcinogenesis such as angiogenesis, proliferation and apoptosis. Several single nucleotide polymorphisms (SNPs) in MMPs and MTs that affect genes expression have been associated with cancer risk, including breast, lung and colon. METHODS: The study group consisted of 648 unselected patients (299 with breast cancer, 199 with lung cancer, 150 with colon cancer) and 648 unaffected individuals. Five SNPs, rs1799750 in MMP-1, rs243865 in MMP-2, rs11568818 in MMP-7, rs2252070 in MMP-13 and rs28366003 in MT2A were genotyped and serum zinc (Zn) level was measured. The cancer risk was calculated using multivariable logistic regression with respect to Zn. RESULTS: None of the 5 tested polymorphisms showed a correlation with cancer risk in studied groups, although for MMP-2, MMP-7 and MT2A non-significant differences in genotypes frequencies among cases and controls were observed. CONCLUSIONS: Analyses of polymorphisms, rs1799750 in MMP-1, rs243865 in MMP-2, rs11568818 in MMP-7, rs2252070 in MMP-13 and rs28366003 in MT2A in relation to serum Zn level did not show significant association with breast, lung and colon cancer risk among polish patients. Further studies are needed to verify this observation.