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Reactive oxygen species (ROS) mediates the mitochondrial‐dependent apoptosis induced by transforming growth factor ß in fetal hepatocytes
Author(s) -
HERRERA BLANCA,
ÁLVAREZ ALBERTO. M.,
SÁNCHEZ ARÁNZAZU,
FERNÁNDEZ MARGARITA,
RONCERO CÉSAR,
BENITO MANUEL,
FABREGAT ISABEL
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0267com
Subject(s) - cytochrome c , reactive oxygen species , apoptosis , biology , microbiology and biotechnology , mitochondrion , programmed cell death , transforming growth factor , bcl xl , cytochrome , transforming growth factor beta , caspase 3 , biochemistry , enzyme
Treatment of fetal rat hepatocytes with transforming growth factor beta (TGF‐ß) is followed by apoptotic cell death. Analysis of radical oxygen species (ROS) content and mitochondrial transmembrane potential (Δψ m ), using specific fluorescent probes in FACScan and confocal microscopy, showed that TGF‐ß mediates ROS production that precedes the loss of Δψ m , the release of cytochrome c, and the activation of caspase 3. TGF‐ß induces a decrease in the protein and mRNA levels of bcl‐x L , an antiapoptotic member of the Bcl‐2 family. In contrast, there is no change in the expression and/or translocation of Bax, a proapoptotic member of the same family. EGF maintains Bcl‐x L , preventing Δψ m collapse and release of cytochrome c. The presence of radical scavengers blocks the decrease in bcl‐x L levels, Δψ m collapse, cytochrome c release, and activation of caspase 3; in contrast, the presence of glutathione synthesis inhibitors such as BSO accentuated the effect. The incubation of fetal hepatocytes in the presence of ter‐butyl‐hydroperoxide alone produces a decrease in bcl‐x L . These results indicate that during the apoptosis mediated by TGF‐ß in fetal hepatocytes, ROS may be responsible for the decrease in bcl‐x L mRNA levels that precedes the loss of Δψ m , the release of cytochrome c , and the activation of caspase 3, culminating in cell death.—Herrera, B., Alvarez, A. M., Sanchez, A., Fernandez, M., Roncero, C., Benito, M., Fabregat, I. Reactive oxygen species (ROS) mediates the mitochondrial‐dependent apoptosis induced by transforming growth factor ß in fetal hepatocytes. FASEB J. 15, 741‐751 (2001)