Abstract
The 1,10-orthophenanthroline (OP)-Cu(2+) combination, one generally used reactive oxygen species (ROS) generation system, is known to induce cell apoptosis, but the mechanism of ROS generation in this process remains unclear. Here we found that in the presence of 5 microM Cu(2+), OP inhibited histone acetyltransferase (HAT) activity, resulting in decreased acetylation in both histone H3 and H4. This inhibition of histone acetylation and HAT activity was significantly attenuated by preventing or scavenging ROS generation with the Cu(2+) chelator of bathocuproine disulfonate, or the antioxidants of N-acetyl-cysteine and mannitol, respectively, indicating the involvement of ROS generation in OP-Cu(2+) -induced histone hypoacetylation. At the same time, this ROS generation is found to be involved in OP-Cu(2+) -induced apoptosis in human hepatoma Hep3B cells. The important role of histone hypoacetylation in the induction of apoptosis was also proven by the marked diminution of apoptosis by 100 nM trichostatin A, a specific inhibitor of histone deacetylase, or the overexpression of p300, an HAT protein. Collectively, these observations suggest that histone hypoacetylation represents one unrevealed mechanism involved in the in vivo function of OP-Cu(2+) -generated ROS, at least in their induction of cell apoptosis.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.