title: Activation of Bak in ultrasound-induced, JNK- and p38-independent apoptosis and its inhibition by Bcl-2.
abstract: The molecular mechanisms underlying ultrasound-induced apoptosis remain poorly understood. We have demonstrated that in Jurkat cells, the over-expression of the anti-apoptotic protein Bcl-2 inhibited ultrasound-induced apoptosis, but not necrosis. Inhibition of caspase activity also protected the cells from apoptosis, but not from necrosis, showing the involvement of different mechanisms in ultrasound-induced apoptosis and necrosis. Bak, a pro-apoptotic member of the Bcl-2 family proteins, was activated by ultrasound and its activation was completely inhibited by Bcl-2 over-expression, but not by caspase inhibition. Antioxidant N-acetyl cysteine did not protect the cells from ultrasound-induced apoptosis or necrosis, nor did the inhibition of either c-Jun N-terminal kinase or p38, key factors in the radical oxygen species (ROS)-mediated cell stress response, suggesting that ROS do not play a crucial role in ultrasound-induced apoptosis. Our results confirm that ultrasound induces apoptosis via a pathway that involves Bak, Bcl-2, and caspases, but not ROS.
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. mkinosit@bwh.harvard.edu
authors.forename: Manabu
authors.initials: M
authors.lastname: Kinoshita
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Eguchi
authors.forename: Kullervo
authors.initials: K
authors.lastname: Hynynen
mesh_terms: D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019169:Jurkat Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D011829:Radiation Dosage; D013010:Sonication; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C494772:BAK1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases