(1) the mechanisms and outcomes of doxorubicin (DOX)-dependent toxicity upon changed intracellular zinc (Zn) concentrations in the cardiomyocytes obtained from human-induced pluripotent stem cells (hiPCS-CMs) were investigated; (2) cells exposed to the DOX were pretreated or cotreated with zinc pyrythione (ZnPyr) and various cellular endpoints and mechanisms were analyzed via cytometric methods; (3) both DOX concentrations (0.3 and 1 µM) induced a concentration-dependent loss of viability, an activation of autophagy, cell death, and the appearance of senescence. These phenotypes were preceded by an oxidative burst, DNA damage, and a loss of mitochondrial and lysosomal integrity. Furthermore, in DOX-treated cells, proinflammatory and stress kinase signaling (in particular, JNK and ERK) were upregulated upon the loss of free intracellular Zn pools. Increased free Zn concentrations proved to have both inhibitory and stimulatory effects on the investigated DOX-related molecular mechanisms, as well as on signaling pathways on the resulting cell fates; and (4) free intracellular Zn pools, their status, and their elevation might have, in a specific context, a pleiotropic impact upon DOX-dependent cardiotoxicity.

• Klíčová slova
• MAPK, doxorubicin, hiPCS-CMs, senescence, zinc,
• MeSH
• buněčná smrt MeSH
• doxorubicin farmakologie   MeSH
• indukované pluripotentní kmenové buňky * MeSH
• kardiomyocyty metabolismus   MeSH
• lidé MeSH
• zinek * metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• doxorubicin MeSH
• zinek * MeSH

Micronutrient malnutrition is a global health issue and needs immediate attention. Over two billion people across the globe suffer from micronutrient malnutrition. The widespread zinc (Zn) deficiency in soils, poor zinc intake by humans in their diet, low bioavailability, and health consequences has led the research community to think of an economic as well as sustainable strategy for the alleviation of zinc deficiency. Strategies like fortification and diet supplements, though effective, are not economical and most people in low-income countries cannot afford them, and they are the most vulnerable to Zn deficiency. In this regard, the biofortification of staple food crops with Zn has been considered a useful strategy. An agronomic biofortification approach that uses crop fertilization with Zn-based fertilizers at the appropriate time to ensure grain Zn enrichment has been found to be cost-effective, easy to practice, and efficient. Genetic biofortification, though time-consuming, is also highly effective. Moreover, a Zn-rich genotype once developed can also be used for many years without any recurring cost. Hence, both agronomic and genetic biofortification can be a very useful tool in alleviating Zn deficiency.

• Klíčová slova
• agronomic biofortification, genetic biofortification, malnutrition, micronutrient, zinc,
• MeSH
• biofortifikace metody   MeSH
• fortifikované potraviny normy   MeSH
• lidé MeSH
• nutriční stav MeSH
• podvýživa dietoterapie   patofyziologie   MeSH
• průmyslová hnojiva analýza   MeSH
• půda chemie   MeSH
• zemědělské plodiny genetika   MeSH
• zinek chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• průmyslová hnojiva MeSH
• půda MeSH
• zinek MeSH

Changes in zinc content and dysregulated zinc homeostatic mechanisms have been recognized in several solid malignancies such as prostate cancer, breast cancer, or pancreatic cancer. Moreover, it has been shown that zinc serum and/or tissue levels are altered in melanoma with varying effects on melanoma development and biology. This study was conducted to explore the effects of acute increases of intracellular zinc in a set of melanoma tissue explants obtained from clinical samples. Measurements of their zinc content showed an extant heterogeneity in total and free intracellular zinc pools associated with varying biological behavior of individual cells, e.g., autophagy levels and propensity to cell death. Use of zinc pyrithione elevated intracellular zinc in a short time frame which resulted in marked changes in mitochondrial activity and lysosomes. These alterations were accompanied by significantly enhanced autophagy flux and subsequent cell demise in the absence of typical apoptotic cell death markers. The present results show for the first time that acutely increased intracellular zinc in melanoma cells specifically enhances their autophagic activity via mitochondria and lysosomes which leads to autophagic cell death. While biologically relevant, this discovery may contribute to our understanding and exploration of zinc in relation to autophagy as a means of controlling melanoma growth and survival.

• Klíčová slova
• autophagy, cell death, lysosomes, melanoma, mitochondria, zinc,
• MeSH
• apoptóza MeSH
• autofagie * účinky léků   MeSH
• buněčná smrt MeSH
• časové faktory MeSH
• intracelulární membrány účinky léků   metabolismus   MeSH
• intracelulární prostor metabolismus   MeSH
• lidé MeSH
• lyzozomy metabolismus   MeSH
• melanocyty účinky léků   metabolismus   MeSH
• melanom metabolismus   MeSH
• mitochondrie účinky léků   metabolismus   MeSH
• nádorové buněčné linie MeSH
• proliferace buněk MeSH
• zinek metabolismus   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• zinek MeSH

Zinc ions are essential cofactors of a wide range of enzymes, transcription factors, and other regulatory proteins. Moreover, zinc is also involved in cellular signaling and enzymes inhibition. Zinc dysregulation, deficiency, over-supply, and imbalance in zinc ion transporters regulation are connected with various diseases including cancer. A zinc ion pool is maintained by two types of proteins: (i) zinc-binding proteins, which act as a buffer and intracellular donors of zinc and (ii) zinc transporters responsible for zinc fluxes into/from cells and organelles. The decreased serum zinc ion levels have been identified in patients suffering from various cancer diseases, including head and neck tumors and breast, prostate, liver, and lung cancer. On the contrary, increased zinc ion levels have been found in breast cancer and other malignant tissues. Zinc metalloproteomes of a majority of tumors including brain ones are still not yet fully understood. Current knowledge show that zinc ion levels and detection of certain zinc-containing proteins may be utilized for diagnostic and prognostic purposes. In addition, these proteins can also be promising therapeutic targets. The aim of the present work is an overview of the importance of zinc ions, zinc transporters, and zinc-containing proteins in brain tumors, which are, after leukemia, the second most common type of childhood cancer and the second leading cause of death in children after accidents.

• Klíčová slova
• Cancer, Childhood brain tumors, Metallothioneins, Zinc metalloenzymes, Zinc transporters,
• MeSH
• biologické modely MeSH
• cílená molekulární terapie MeSH
• dítě MeSH
• lidé MeSH
• nádorové proteiny metabolismus   MeSH
• nádory mozku diagnóza   metabolismus   MeSH
• zinek metabolismus   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• nádorové proteiny MeSH
• zinek MeSH