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

Abstract

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 were 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.

• Authors: Eugenio Barone, Fabio Di Domenico, Giovanna Cenini, Rukhsana Sultana, Chiara Cini, Paolo Preziosi, Marzia Perluigi, Cesare Mancuso, D Allan Butterfield
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1812 Issue 4 Pg. 480-7 (Apr 2011) ISSN: 0006-3002 [Print] Netherlands
• PMID: 21241799 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Phosphothreonine
• Phosphoserine
• Phosphotyrosine
• Oxidoreductases Acting on CH-CH Group Donors
• biliverdin reductase
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (enzymology, genetics, physiopathology)
• Brain (enzymology)
• Cognition
• Enzyme Activation
• Female
• Humans
• Male
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Oxidative Stress
• Oxidoreductases Acting on CH-CH Group Donors (genetics, metabolism)
• Phosphoserine (metabolism)
• Phosphothreonine (metabolism)
• Phosphotyrosine (metabolism)
• Up-Regulation