Role of 4-hydroxynonenal in stress-mediated apoptosis signaling.
In this mini review we summarize recent studies from our laboratory, which show the involvement of 4-hydroxynonenal (4-HNE) in cell cycle signaling. We demonstrate 4-HNE induced apoptosis in various cell lines is accompanied with c-Jun-N-terminal kinase and caspase-3 activation. Cells exposed to mild, transient, heat or oxidative stress acquire capacity to exclude intracellular 4-HNE at a faster rate by inducing hGST5.8 which conjugate 4-HNE to GSH, and RLIP76 which mediates the ATP-dependent transport of the GSH-conjugate of 4-HNE. The cells preconditioned with mild transient stress acquire resistance to H(2)O(2) and 4-HNE induced apoptosis by excluding intracellular 4-HNE at an accelerated pace. Furthermore, a decrease in intracellular concentration of 4-HNE achieved by transfecting cells with mGSTA4-4 or hGSTA4-4 results in a faster growth rate. These studies strongly suggest a role of 4-HNE in stress mediated signaling.
Awasthi
Yogesh C
YC
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, 551 Basic Science Building, Galveston, TX 77555-0647, USA. ycawasth@utmb.ca
Sharma
Rajendra
R
Cheng
J Z
JZ
Yang
Yusong
Y
Sharma
Abha
A
Singhal
Sharad S
SS
Awasthi
Sanjay
S
D018528:ATP-Binding Cassette Transporters; D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000276:immunology / Q000502:physiology*; D002352:Carrier Proteins / Q000276:immunology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D020690:GTPase-Activating Proteins; D005982:Glutathione Transferase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000378:metabolism
D018528:ATP-Binding Cassette Transporters; D000447:Aldehydes; D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; C095637:RALBP1 protein, human; D018808:Transcription Factor AP-1; D006861:Hydrogen Peroxide; D005982:Glutathione Transferase; D020928:Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; C027576:4-hydroxy-2-nonenal