Biliverdin reductase-A protein levels and activity in the brains of subjects with Alzheimer disease and mild cognitive impairment

Eugenio Barone (1, 2) , Fabio Di Domenico (1, 3) , Giovanna Cenini (1) , Rukhsana Sultana (1) , Chiara Cini (3) , Paolo Preziosi (2) , Marzia Perluigi (3) , Cesare Mancuso (2) , D. Allan Butterfield (1)

1 Department of Chemistry
2 Catholic University School of Medicine
3 Department of Biochemical Sciences "Rossi Fanelli"

Biliverdin reductase-A is a pleiotropic enzyme involved not only in the reduction of biliverdin-IX -alpha into bilirubin-IX-alpha, but also in the regulation of glucose metabolism and cell growth secondary to its serine/threonine/tyrosine kinase activity. Together with heme oxygenase, whose metabolic role is to degrade heme into biliverdin-IX-alpha, it forms a powerful system involved in the cell stress response during neurodegenerative disorders. In this paper, an up-regulation of the biliverdin reductase-A protein levels was found in the hippocampus of the subjects with Alzheimer disease and arguably its earliest form, mild cognitive impairment. Moreover a significant reduction in the phosphorylation of serine, threonine and tyrosine residues of biliverdin reductase-A was found, and this was paralleled by a marked reduction in its reductase activity. Interestingly, the levels of both total and phosphorylated biliverdin reductase-A was unchanged as well as its enzymatic activity in the cerebella. These results demonstrated a dichotomy between biliverdin reductase-A protein levels and activity in the hippocampus of subjects affected by Alzheimer disease and mild cognitive impairment, and this effect likely is attributable to a reduction in the phosphorylation of serine, threonine and tyrosine residues of biliverdin reductase-A. Consequently, not just the increased levels of biliverdin reductase-A, but also its changed activity and phosphorylation state, should be taken into account when considering potential biomarkers for Alzheimer disease and mild cognitive impairment.

Mots clés: AD; BVR; HO; MCI; pSer/Thre; pTyr; Alzheimer Disease; Biliverdin Reductase; Cerebellum; Hippocampus; Mild Cognitive Impairment; Oxidative Stress

Domaines: Biochimie, Biologie Moléculaire

Eugenio Barone, Fabio Di Domenico, Giovanna Cenini, Rukhsana Sultana, Chiara Cini, et al.. Biliverdin reductase-A protein levels and activity in the brains of subjects with Alzheimer disease and mild cognitive impairment. Biochimica et Biophysica Acta - Molecular Basis of Disease, 2011, 1812 (4), pp.480. ⟨10.1016/j.bbadis.2011.01.005⟩. ⟨hal-00670753⟩