Glutathione
S-transferase π Protects Serum Depletion-induced Cell Death by Inhibiting
ASK1-MKK7-JNK Pathway in the 293 Cells
YIN Zhi-Min, LIU Ai-Hua, JIANG Yong*
( Department of Pathophysiology and Key Lab for Shock
and Microcirculation of PLA, The First Military Medical University, Guangzhou 510515,
China )
Abstract Glutathione
S transferase π(GSTπ) protects cells from death by altering intracellular
oxidative stress. In order to understand the mechanism of GSTπ protection, a
cell death model induced by serum depletion as the stress was established.
Cotransfection of apoptosis signal regulating kinase 1 (ASK1) and GSTπ cDNA was
performed to elucidate the impact of GSTπ on ASK1 activity, as well as on its
downstream signals, MKK7 and JNK, and to elucidate the potential protection of
GSTπ on 293 cell death induced by serum depletion. The dominant negative mutant
of JNK was used to explore if the blocking of the JNK pathway led to cell death
inhibition. It was found that GSTπ had a dose-dependent inhibitory effect on
activation induced by serum depletion, and also on inhibition both on MKK7 and
JNK. Intracellular expression of GSTπ significantly inhibited serum
depletion-induced cell death. Blocking the JNK pathway by transfection of a
dominant negative form of JNK (JNK APF) brought about significant
inhibition of cell death induced by serum depletion with an inhibiting rate as
high as 15%. All the results suggest that the mechanism of GSTπ protection on
serum depletion induced cell death works through an ASK1-MKK7-JNK pathway.
Key words glutathione S-transferase； cell death； stress； signal transduction； mitogen-activated protein
kinases
*Corresponding author： Tel, 86-20-85148231； Fax, 86-20-87705671； e-mail, [email protected]