Motexafin gadolinium enhances p53-Mdm2 interactions, reducing p53 and downstream targets in lymphoma cell lines.
Motexafin gadolinium enhances p53-Mdm2 interactions, reducing p53 and downstream targets in lymphoma cell lines.
复制标题
DOI：
--
复制
发表时间：
2010-04
影响因子：
2
通讯作者：
Amareshwar T. K. Singh;A. Evens;S. Prachand;L. Gordon
中科院分区：
文献类型：
--
作者：
Amareshwar T. K. Singh;A. Evens;S. Prachand;L. Gordon
BACKGROUND Loss of p53 renders cells more susceptible to acute oxidant stress induced by oxidant-generating agents such as motexafin gadolinium (MGd). We hypothesized that reactive oxygen species (ROS)-generating MGd results in low-level p53 expression, making cells more susceptible to oxidant stress. MATERIALS AND METHODS Lymphoma cells were incubated with different concentrations of MGd with or without zinc (Zn) and ascorbate, and ROS, apoptosis, proteins, and oxidant genes were measured. RESULTS MGd, with ascorbate and Zn, induced apoptosis in lymphoma cells. This was accompanied by reduction of p53 protein but not message, and by reduction of p53 downstream targets p21, glutathione peroxidase 1 (GPx1), and p53 up-regulated modulator of apoptosis (PUMA). p53 protein reduction was reversed by MG132, and nutlin-3. CONCLUSION Our data are consistent with a pathway of cell death that is independent of p53-mediated induction of PUMA; the cellular response to reduce p53 represents a cell survival adjustment to ROS-mediated stress.
