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Toxicology and Cancer Biology Faculty Publications

2011

Articles 1 - 3 of 3

Full-Text Articles in Medicine and Health Sciences

Manganese Superoxide Dismutase: Guardian Of The Powerhouse, Aaron K. Holley, Vasudevan Bakthavatchalu, Joyce M. Velez-Roman, Daret K. St. Clair Oct 2011

Manganese Superoxide Dismutase: Guardian Of The Powerhouse, Aaron K. Holley, Vasudevan Bakthavatchalu, Joyce M. Velez-Roman, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

The mitochondrion is vital for many metabolic pathways in the cell, contributing all or important constituent enzymes for diverse functions such as β-oxidation of fatty acids, the urea cycle, the citric acid cycle, and ATP synthesis. The mitochondrion is also a major site of reactive oxygen species (ROS) production in the cell. Aberrant production of mitochondrial ROS can have dramatic effects on cellular function, in part, due to oxidative modification of key metabolic proteins localized in the mitochondrion. The cell is equipped with myriad antioxidant enzyme systems to combat deleterious ROS production in mitochondria, with the mitochondrial antioxidant enzyme manganese …


Phenethyl Isothiocyanate Exhibits Antileukemic Activity In Vitro And In Vivo By Inactivation Of Akt And Activation Of Jnk Pathways, N. Gao, Amit Budhraja, S. Cheng, E.-H. Liu, J. Chen, Z. Yang, D. Chen, Zhuo Zhang, Xianglin Shi Apr 2011

Phenethyl Isothiocyanate Exhibits Antileukemic Activity In Vitro And In Vivo By Inactivation Of Akt And Activation Of Jnk Pathways, N. Gao, Amit Budhraja, S. Cheng, E.-H. Liu, J. Chen, Z. Yang, D. Chen, Zhuo Zhang, Xianglin Shi

Toxicology and Cancer Biology Faculty Publications

Effects of phenethyl isothiocyanate (PEITC) have been investigated in human leukemia cells (U937, Jurkat, and HL-60) as well as in primary human acute myeloid leukemia (AML) cells in relation to apoptosis and cell signaling events. Exposure of cells to PEITC resulted in pronounced increase in the activation of caspase-3, -8, -9, cleavage/degradation of PARP, and apoptosis in dose- and time-dependent manners. These events were accompanied by the caspase-independent downregulation of Mcl-1, inactivation of Akt, as well as activation of Jun N-terminal kinase (JNK). Inhibition of PI3K/Akt by LY294002 significantly enhanced PEITC-induced apoptosis. Conversely, enforced activation of Akt by a constitutively …


P53 Regulates Oxidative Stress-Mediated Retrograde Signaling: A Novel Mechanism For Chemotherapy-Induced Cardiac Injury, Joyce M. Velez, Sumitra Miriyala, Ramaneeya Nithipongvanitch, Teresa Noel, Chotiros D. Plabplueng, Terry Oberley, Paiboon Jungsuwadee, Holly Van Remmen, Mary Vore, Daret K. St Clair Mar 2011

P53 Regulates Oxidative Stress-Mediated Retrograde Signaling: A Novel Mechanism For Chemotherapy-Induced Cardiac Injury, Joyce M. Velez, Sumitra Miriyala, Ramaneeya Nithipongvanitch, Teresa Noel, Chotiros D. Plabplueng, Terry Oberley, Paiboon Jungsuwadee, Holly Van Remmen, Mary Vore, Daret K. St Clair

Toxicology and Cancer Biology Faculty Publications

The side effects of cancer therapy on normal tissues limit the success of therapy. Generation of reactive oxygen species (ROS) has been implicated for numerous chemotherapeutic agents including doxorubicin (DOX), a potent cancer chemotherapeutic drug. The production of ROS by DOX has been linked to DNA damage, nuclear translocation of p53, and mitochondrial injury; however, the causal relationship and molecular mechanisms underlying these events are unknown. The present study used wild-type (WT) and p53 homozygous knock-out (p53(-/-)) mice to investigate the role of p53 in the crosstalk between mitochondria and nucleus. Injecting mice with DOX (20 mg/kg) causes oxidative stress …