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Inhibition of the adenine nucleotide translocator by N-acetyl perfluorooctane s...
O'Brien, Timothy M.; Oliveira, Paulo J.; Wallace, Kendall B.N-alkyl perfluorooctane sulfonamides have been widely used as surfactants on fabrics and papers, fire retardants, and anti-corrosion agents, among many other commercial applications. The global distribution and environmental persistence of these compounds has generated considerable interest regarding potential toxic effects. We have previously reported that perfluorooctanesulfonamidoacetate (FOSAA) and N-ethylp...
Hyperglycemia decreases mitochondrial function: The regulatory role of mitochon...
Palmeira, Carlos M.; Rolo, Anabela P.; Berthiaume, Jessica; Bjork, James A.; Wallace, Kendall B.Increased generation of reactive oxygen species (ROS) is implicated in "glucose toxicity" in diabetes. However, little is known about the action of glucose on the expression of transcription factors in hepatocytes, especially those involved in mitochondrial DNA (mtDNA) replication and transcription. Since mitochondrial functional capacity is dynamically regulated, we hypothesized that stressful conditions of hy...
Vital imaging of H9c2 myoblasts exposed to tert-butylhydroperoxide--characteriz...
Sardão, Vilma A.; Oliveira, Paulo J.; Holy, Jon; Oliveira, Catarina R.; Wallace, Kendall B.Background When exposed to oxidative conditions, cells suffer not only biochemical alterations, but also morphologic changes. Oxidative stress is a condition induced by some pro-oxidant compounds, such as by tert-butylhydroperoxide (tBHP) and can also be induced in vivo by ischemia/reperfusion conditions, which is very common in cardiac tissue. The cell line H9c2 has been used as an in vitro cellular model for ...
Esterification Prevents Induction of the Mitochondrial Permeability Transition ...
O'Brien, Timothy M.; Carlson, Robert M.; Oliveira, Paulo J.; Wallace, Kendall B.N-Alkyl perfluorooctane sulfonamides have been widely used as surfactants on fabrics and papers, fire retardants, and anticorrosion agents, among many other commercial applications. The broad use, global distribution, and environmental persistence of these compounds has generated considerable interest regarding potentially toxic effects. We have previously reported that perfluorooctanesulfonamidoacetate (FOSAA)...
Carvedilol-mediated antioxidant protection against doxorubicin-induced cardiac ...
Oliveira, Paulo J.; Bjork, James A.; Santos, Maria S.; Leino, Richard L.; Froberg, M. Kent; Moreno, António J.; Wallace, Kendall B.The cardiotoxicity associated with doxorubicin (DOX) therapy limits the total cumulative dose and therapeutic success of active anticancer chemotherapy. Cardiac mitochondria are implicated as primary targets for DOX toxicity, which is believed to be mediated by the generation of highly reactive free radical species of oxygen from complex I of the mitochondrial electron transport chain. The objective of this stu...
Role of mitochondrial dysfunction in combined bile acid-induced cytotoxicity: t...
Rolo, Anabela P.; Palmeira, Carlos M.; Holy, Jon M.; Wallace, Kendall B.The goal of this investigation was to determine whether chenodeoxycholic acid (CDCA)-induced apoptosis is prevented by ursodeoxycholic acid (UDCA) or tauroursodeoxycholic acid (TUDC) and to characterize the involvement of mitochondria in the process. Cultured human HepG2 cells were treated in a dose- and time-dependent protocol in order to establish a sufficiently low exposure to CDCA that causes apoptosis but ...
Mitochondrially mediated synergistic cell killing by bile acids
Rolo, Anabela P.; Palmeira, Carlos M.; Wallace, Kendall B.The accumulation of endogenous bile acids contributes to hepatocellular damage during cholestatic liver disease. To examine the controversy regarding the therapeutic use of ursodeoxycholate (UDCA) in cholestatic patients, we investigated the possible cytoprotection or synergistic effects of UDCA against chenodeoxycholate (CDCA)-induced injury to isolated rat hepatocytes. Our aim was to investigate the role of t...
Interactions of combined bile acids on hepatocyte viability: cytoprotection or ...
Rolo, Anabela P.; Palmeira, Carlos M.; Wallace, Kendall B.Cholestasis results from hepatocyte dysfunction due to the accumulation of bile acids in the cell, many of which are known to be cytotoxic. Recent evidence implicates competitive antagonism of key cytotoxic responses as the mechanism by which certain therapeutic bile acids might afford cytoprotection against cholestasis. In this work, we compare the relative cytotoxicity of bile acids in terms of dose- and time...
Doxorubicin-induced persistent oxidative stress to cardiac myocytes
Zhou, Shaoyu; Palmeira, Carlos M.; Wallace, Kendall B.We recently reported a cardioselective and cumulative oxidation of cardiac mitochondrial DNA (mtDNA) following subchronic administration of doxorubicin to rats. The mtDNA adducts persist for up to 5 weeks after cessation of doxorubicin treatment. Since the evidence suggests that this persistence of mtDNA adducts cannot be attributed to a lack of repair and replication, we investigated whether it might reflect a...
Tamoxifen Inhibits Induction of the Mitochondrial Permeability Transition by Ca...
Custódio, José B. A.; Moreno, António J. M.; Wallace, Kendall B.Tamoxifen (TAM) is a synthetic, nonsteroidal antiestrogenic agent that is widely prescribed in the treatment of estrogen-dependent neoplasias, including breast cancer. The mechanism of action has yet to be defined, but likely is independent of estrogen receptor binding. In light of its high lipophilicity and peroxyl radical scavenging activities, we hypothesized that TAM might be an effective inhibitor of the m...
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