Trehalose and 6-aminohexanoic acid stabilize and renature glucose-6-phosphate dehydrogenase inactivated by glycation and by guanidinium hydrochloride.
A number of naturally occurring small organic molecules, primarily involved in maintaining osmotic pressure in the cell, display chaperone-like activity, stabilizing the native conformation of proteins and protecting them from various kinds of stress. Most of them are sugars, polyols, amino acids or methylamines. In addition to their intrinsic protein-stabilizing activity, these small organic stress molecules regulate the activity of some molecular chaperones, and may stabilize the folded state of proteins involved in unfolding or in misfolding diseases, such as Alzheimer's and Parkinson's diseases, or alpha1-antitrypsin deficiency and cystic fibrosis, respectively. Similar to molecular chaperones, most of these compounds have no substrate specificity, but some specifically stabilize certain proteins, e.g., 6-aminohexanoic acid (AHA) stabilizes apolipoprotein A. In the present work, the capacity of 6-aminohexanoic acid to stabilize non-specifically other proteins is demonstrated. Both trehalose and AHA significantly protect glucose-6-phosphate dehydrogenase (G6PD) against glycation-induced inactivation, and renatured enzyme already inactivated by glycation and by guanidinium hydrochloride (GuHCl). To the best of our knowledge, there are no data on the effect of these compounds on protein glycation. The correlation between the recovery of enzyme activity and structural changes indicated by fluorescence spectroscopy and Western blotting contribute to better understanding of the protein stabilization mechanism.
Ganea
Elena
E
Nuffield Laboratory of Ophthalmology, Oxford University, Oxford OX2 6AW, UK.
Harding
John J
JJ
D015119:Aminocaproic Acid / Q000494:pharmacology*; D000817:Anilino Naphthalenesulfonates / Q000737:chemistry; D015153:Blotting, Western; D005947:Glucose / Q000378:metabolism*; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors*; D019791:Guanidine / Q000494:pharmacology*; D011489:Protein Denaturation; D017510:Protein Folding; D013050:Spectrometry, Fluorescence; D014199:Trehalose / Q000494:pharmacology*
D000817:Anilino Naphthalenesulfonates; C027132:1-anilino-8-naphthalenesulfonate; D014199:Trehalose; D005954:Glucosephosphate Dehydrogenase; D005947:Glucose; D019791:Guanidine; D015119:Aminocaproic Acid