MnSOD Lysine 68 acetylation leads to cisplatin and doxorubicin resistance due to aberrant mitochondrial metabolism.

Manganese superoxide dismutase (MnSOD) acetylation (Ac) has been shown to be a key post-translational modification important in the regulation of detoxification activity in various disease models. We have previously demonstrated that MnSOD lysine-68 (K68) acetylation (K68-Ac) leads to a change in function from a superoxide-scavenging homotetramer to a peroxidase-directed monomer. Here, we found that estrogen receptor positive (ER+) breast cancer cell lines (MCF7 and T47D), selected for continuous growth in cisplatin (CDDP) and doxorubicin (DXR), exhibited an increase in MnSOD-K68-Ac.

Lysine 68 acetylation directs MnSOD as a tetrameric detoxification complex versus a monomeric tumor promoter.

Manganese superoxide dismutase (MnSOD) functions as a tumor suppressor; however, once tumorigenesis occurs, clinical data suggest MnSOD levels correlate with more aggressive human tumors, implying a potential dual function of MnSOD in the regulation of metabolism. Here we show, using in vitro transformation and xenograft growth assays that the MnSOD-K68 acetylation (Ac) mimic mutant (MnSOD) functions as a tumor promoter. Interestingly, in various breast cancer and primary cell types the expression of MnSOD is accompanied with a change of MnSOD's stoichiometry from a known homotetramer complex to a monomeric form.

The freedom to heal: nonrigid immobilization by a halo orthosis.

Halo orthoses present a paradox. On the one hand, the nominally rigid immobilization they provide to the head aims to remove loads on the cervical spine following injury or surgery, and the devices are retightened routinely to maintain this. On the other hand, bone growth and remodeling are well known to require mechanical stressing.