title: A short report: PAMM, a novel antioxidant protein, induced by oxidative stress.
abstract: 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.
authors.affiliation: Department of Mineralized Tissue Biology, The Forsyth Institute, 245 First Street, Cambridge, MA 02142, USA; School of Pharmaceutical Science, Kunming Medical University, 1168 West Chunrong Road, Kunming 650500, China. Electronic address: yxu@forsyth.org.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Mineralized Tissue Biology, The Forsyth Institute, 245 First Street, Cambridge, MA 02142, USA; Spaulding-Harvard SCI Model System, Spaulding Rehabilitation Hospital, 300 1st Ave, Charlestown, MA 02129, USA; Department of Physical Medicine and Rehabilitation, Harvard Medical School, 25 Shattuck St, Boston, MA 02115, USA. Electronic address: leslie.morse@mgh.harvard.edu.
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Morse
authors.affiliation: Department of Pediatric Clinic, Preventive and Community Dentistry, School of Dentistry of Ribeirao Preto, University of Sao Paulo, Sao Paulo 05508, Brazil. Electronic address: raquel@forp.usp.br.
authors.forename: Raquel Assed Bezerra
authors.initials: RAB
authors.lastname: da Silva
authors.affiliation: School of Pharmaceutical Science, Kunming Medical University, 1168 West Chunrong Road, Kunming 650500, China. Electronic address: wangdianhuakm@126.com.
authors.forename: Dianhua
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Mineralized Tissue Biology, The Forsyth Institute, 245 First Street, Cambridge, MA 02142, USA; Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, 188 Longwood Ave, Boston, MA 02115, USA. Electronic address: rbattaglino@forsyth.or.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Battaglino
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015519:Bone Density; D002478:Cells, Cultured; D004967:Estrogens / Q000502:physiology; D005260:Female; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D010052:Ovariectomy; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D000975:Antioxidants; D004967:Estrogens; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C555781:PRXL2A protein, human; D016173:Macrophage Colony-Stimulating Factor; D054464:Peroxiredoxins; D051057:Proto-Oncogene Proteins c-akt
keywords: Antioxidant; Bone loss; Ovariectomy; Oxidative stress; PAMM