A short report: PAMM, a novel antioxidant protein, induced by oxidative stress

• We previously identified, characterized and proved PAMM is a novel antioxidant protein that regulates osteoclast formation and activity via modulation of ROS production in vitro.
• PAMM expression is induced by oxidative stress in vivo and in vitro.
• PAMM expression in osteoclasts is stimulated by estrogen and is mediated by Akt phosphorylation.
• PAMM may be a potential candidate for Akt-mediated protection against oxidative stress and bone loss induced by estrogen deficiency.

Reactive oxygen species (ROS) play a central role in estrogen deficiency-induced bone loss. We previously identified and characterized a novel member of the Peroxiredoxin (PRX) like 2 family that we called PAMM: Peroxiredoxin Activated in M-CSF stimulated Monocytes, a redox regulatory protein that modulates osteoclast differentiation in vitro. In this study, we report increased PAMM expression in H2O2-treated cells and in bones from ovariectomized (OVX) mice 4 weeks after surgery, models for oxidative stress in vitro and in vivo, respectively. We also detected increased PAMM abundance and phosphorylated Akt in OVX mice treated with estrogen. In addition, Wortmannin, a specific PI3Kinase inhibitor and Rapamycin, an inhibitor of the PI3Kinase/Akt pathway, blocked Akt phosphorylation and stimulation of PAMM expression by M-CSF. These results indicate that M-CSF-induced PAMM expression is mediated by Akt phosphorylation. Our data also suggest that estrogen-induced PAMM expression is mediated by phosphorylation of Akt. These findings point to PAMM as a potential candidate for Akt-mediated protection against oxidative stress.

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