HNE (4-hydroxynonenal ) induces apoptosis via mitochondrial pathway with the involvement of Bcl-2 family members

Bodur, Çağrı and Yılmaz, Sinem and Kütük, Özgür and Başağa, Hüveyda (2007) HNE (4-hydroxynonenal ) induces apoptosis via mitochondrial pathway with the involvement of Bcl-2 family members. In: 15th Euroconference on Apoptosis, Portorož, Slovenia

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One of the most abundant aldehydic components of ox-LDL is 4-Hydroxynonenal (HNE) which exerts various effects on intracellular and extracellular signaling cascades. HNE was demonstrated to be able to induce apoptosis and ROS formation in a dose dependent manner in a number of studies. Several signaling pathways have been shown to be modulated by HNE, including MAP kinases, PKC isoforms, cell cycle regulators, receptor tyrosine kinases and caspases. We have studied MAP kinase and caspase activation pathways in 3T3 fibroblasts in order to shed light on the mechanisms that HNE induces apoptosis. HNE induced early activation of JNK and p38 proteins but downregulated the basal activity of ERK 1/2. We have shown that HNE induced caspase-9 and 3 activation and release of cytochrome c from mitochondria. Overexpression studies and utilization of specific kinase inhibitors indicated that HNE induced apoptosis through activation of JNK and c-Jun/AP-1 protein. We also demonstrated that resveratrol, a widely distributed flavone, may protect against HNE-induced apoptosis through modulation of JNK activation upstream of mitochondrial apoptotic pathway. Activation of AP-1 along with increased c-Jun and phospho-c- Jun levels could be inhibited by pretreatment of cells with resveratrol. Further investigations about the cellular mechanism of apoptotic response to HNE are in progress by a specific focus on the involvement of pro and anti-apoptotic members of Bcl-2 protein family in our laboratory.
Item Type: Papers in Conference Proceedings
Subjects: Q Science > Q Science (General)
R Medicine > R Medicine (General)
Q Science > QP Physiology
Divisions: Faculty of Engineering and Natural Sciences
Depositing User: Çağrı Bodur
Date Deposited: 25 Jul 2009 16:05
Last Modified: 26 Apr 2022 08:50

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