Cadmium(Cd)induces several effects in different tissues,but our knowledge of the toxic effects on organelles is insuffi cient.To observe the progression of Cd effects on organelle structure and function,HuH-7 cells(hu...Cadmium(Cd)induces several effects in different tissues,but our knowledge of the toxic effects on organelles is insuffi cient.To observe the progression of Cd effects on organelle structure and function,HuH-7 cells(human hepatic carcinoma cell line)were exposed to CdCl2 in increasing concentrations(1μM–20μM)and exposure times(2 h–24 h).During Cd treatment,the cells exhibited a progressive decrease in viability that was both time-and dose-dependent.Cd treated cells displayed progressive morphological changes that included cytoplasm retraction and nuclear condensation preceding a total loss of cell adhesion.Treatment with 10μM for 12 h led to irreversible damages.Before these drastic and irreparable damages,treated cells(5μM for 12 h)presented a progressive loss of mitochondrial function and cytoplasm acidifi cation as well as dysfunction and disorganization of microfi laments and endoplasmic reticulum.These damages led to the induction of apoptotic events and an increase in autophagic bodies in the cytoplasm.These results revealed that Cd affects multiple intra-cellular targets that induce alterations in the mitochondria,cytoskeleton,endoplasmic reticulum and acidic compartments,ultimately culminating in cell death via apoptotic and autophagic pathways.展开更多
基金supported by Fundação Carlos Chagas Filho de AmparoàPesquisa do Estado do Rio de Janeiro(E-26/171.315/2004)(E-26/100.470/2007)(E-26/110.921/2008).
文摘Cadmium(Cd)induces several effects in different tissues,but our knowledge of the toxic effects on organelles is insuffi cient.To observe the progression of Cd effects on organelle structure and function,HuH-7 cells(human hepatic carcinoma cell line)were exposed to CdCl2 in increasing concentrations(1μM–20μM)and exposure times(2 h–24 h).During Cd treatment,the cells exhibited a progressive decrease in viability that was both time-and dose-dependent.Cd treated cells displayed progressive morphological changes that included cytoplasm retraction and nuclear condensation preceding a total loss of cell adhesion.Treatment with 10μM for 12 h led to irreversible damages.Before these drastic and irreparable damages,treated cells(5μM for 12 h)presented a progressive loss of mitochondrial function and cytoplasm acidifi cation as well as dysfunction and disorganization of microfi laments and endoplasmic reticulum.These damages led to the induction of apoptotic events and an increase in autophagic bodies in the cytoplasm.These results revealed that Cd affects multiple intra-cellular targets that induce alterations in the mitochondria,cytoskeleton,endoplasmic reticulum and acidic compartments,ultimately culminating in cell death via apoptotic and autophagic pathways.
