A new approach to monitor expression of aldo–keto reductase proteins in mouse tissues

The aldo–keto reductase (AKR) proteins catalyze reduction of diverse aldehydes and play detoxification roles in many organisms. Since many substrates are shared among AKR, it is generally accepted that these enzymes can functionally compensate each other in response to oxidative stress. Their overall abundances are the important factor that partially reflects the capacity of antioxidant and detoxification in tissues. In this study, the strategy was proposed for generation of Pan‐AKR antibodies to recognize most AKR proteins in mouse tissues. Derived from bioinformatic analysis, several consensus peptides with different potential antigenicities were synthesized, conjugated to hemocyanin from keyhole limpets and further delivered to rabbits to generate polyclonal antibodies. Three Pan‐AKR antibodies exhibited the immune specificities and immune sensitivities, Pan‐AKR‐P1 for AKR1B and AKR1C, Pan‐AKR‐P3 for AKR1C and Pan‐AKR‐P4 for all the AKR proteins. Pan‐AKR‐P4 antibody was employed to 2‐DE Western blot to examine the AKR abundances in mouse liver and kidney, resulting in seven immune‐reactive spots from each tissue. Protein identification with MS revealed that most immune‐positive spots were the members of AKR superfamily. Furthermore, Pan‐AKR‐P4 antibody was implemented to compare the different abundances of the AKR proteins in liver and kidney between normal and diabetic mice, suggesting that diabetes did cause some abnormal changes in the AKR protein abundances.

[1]  E. Maser,et al.  Role of human aldo-keto-reductase AKR1B10 in the protection against toxic aldehydes. , 2009, Chemico-biological interactions.

[2]  J Mark Petrash,et al.  Disruption of aldo-keto reductase genes leads to elevated markers of oxidative stress and inositol auxotrophy in Saccharomyces cerevisiae. , 2008, Biochimica et biophysica acta.

[3]  Jun Ma,et al.  Aldo–keto reductase family 1 B10 gene silencing results in growth inhibition of colorectal cancer cells: Implication for cancer intervention , 2007, International journal of cancer.

[4]  Yi Jin,et al.  Aldo-keto reductases and bioactivation/detoxication. , 2007, Annual review of pharmacology and toxicology.

[5]  D. Gonzalez-Dunia,et al.  Borna Disease Virus Blocks Potentiation of Presynaptic Activity through Inhibition of Protein Kinase C Signaling , 2006, PLoS pathogens.

[6]  O. El-Kabbani,et al.  Enzymatic properties of a member (AKR1C20) of the aldo-keto reductase family. , 2006, Biological & pharmaceutical bulletin.

[7]  N. Metreveli,et al.  Development of late-stage diabetic nephropathy in OVE26 diabetic mice. , 2004, Diabetes.

[8]  B. Kemp,et al.  Effect of exercise on protein kinase C activity and localization in human skeletal muscle , 2004, The Journal of physiology.

[9]  C. Mandal,et al.  Chlorogenic acid inhibits Bcr-Abl tyrosine kinase and triggers p38 mitogen-activated protein kinase-dependent apoptosis in chronic myelogenous leukemic cells. , 2004, Blood.

[10]  E. Maser.  Significance of reductases in the detoxification of the tobacco-specific carcinogen NNK. , 2004, Trends in pharmacological sciences.

[11]  T. Penning,et al.  Structure–function of human 3α-hydroxysteroid dehydrogenases: genes and proteins , 2004, Molecular and Cellular Endocrinology.

[12]  J. Cravedi,et al.  Fate of 4-hydroxynonenal in vivo: disposition and metabolic pathways. , 2003, Molecular aspects of medicine.

[13]  Laurent Vergnes,et al.  A cluster of eight hydroxysteroid dehydrogenase genes belonging to the aldo-keto reductase supergene family on mouse chromosome 13 Published, JLR Papers in Press, December 1, 2002. DOI 10.1194/jlr.M200399-JLR200 , 2003, Journal of Lipid Research.

[14]  T. Penning,et al.  The aldo-keto reductase superfamily homepage. , 2003, Chemico-biological interactions.

[15]  R. Bolli,et al.  Aldose Reductase Is an Obligatory Mediator of the Late Phase of Ischemic Preconditioning , 2002, Circulation research.

[16]  N. Palackal,et al.  The Reactive Oxygen Species- and Michael Acceptor-inducible Human Aldo-Keto Reductase AKR1C1 Reduces the α,β-Unsaturated Aldehyde 4-Hydroxy-2-nonenal to 1,4-Dihydroxy-2-nonene* , 2000, The Journal of Biological Chemistry.

[17]  M. Inoue,et al.  Impaired reductive regeneration of ascorbic acid in the Goto-Kakizaki diabetic rat. , 2000, The Biochemical journal.

[18]  Michael E. Burczynski,et al.  Human 3α-hydroxysteroid dehydrogenase isoforms (AKR1C1–AKR1C4) of the aldo-keto reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones , 2000 .

[19]  Mark A. Knepper,et al.  Aldose Reductase-Deficient Mice Develop Nephrogenic Diabetes Insipidus , 2000, Molecular and Cellular Biology.

[20]  D. Lohnes,et al.  Cloning and developmental expression of mouse aldehyde reductase (AKR1A4) , 2000, Mechanisms of Development.

[21]  D. Harrison,et al.  Major differences exist in the function and tissue-specific expression of human aflatoxin B1 aldehyde reductase and the principal human aldo-keto reductase AKR1 family members. , 1999, The Biochemical journal.

[22]  C. Yabe-Nishimura,et al.  Aldose reductase in glucose toxicity: a potential target for the prevention of diabetic complications. , 1998, Pharmacological reviews.

[23]  M. Lewis,et al.  Comparative anatomy of the aldo-keto reductase superfamily. , 1997, The Biochemical journal.

[24]  K. Jung,et al.  ORE, a Eukaryotic Minimal Essential Osmotic Response Element , 1996, The Journal of Biological Chemistry.

[25]  S. Chung,et al.  Tissue-specific expression of two aldose reductase-like genes in mice: abundant expression of mouse vas deferens protein and fibroblast growth factor-regulated protein in the adrenal gland. , 1995, The Biochemical journal.

[26]  D. V. Vander Jagt,et al.  Substrate specificity of human aldose reductase: identification of 4-hydroxynonenal as an endogenous substrate. , 1995, Biochimica et biophysica acta.

[27]  P. Tongaonkar,et al.  A semi‐empirical method for prediction of antigenic determinants on protein antigens , 1990, FEBS letters.

[28]  A. Means,et al.  Calmodulin-induced early-onset diabetes in transgenic mice , 1989, Cell.

[29]  T. Hohman,et al.  Characterization of mRNA and genes for aldose reductase in rat. , 1988, Biochemical and biophysical research communications.

[30]  R. Balaban,et al.  Induction of aldose reductase and sorbitol in renal inner medullary cells by elevated extracellular NaCl. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[31]  E. Butcher,et al.  Lymphoid tissue- and inflammation-specific endothelial cell differentiation defined by monoclonal antibodies. , 1987, Journal of immunology.

[32]  A. Hartmann,et al.  (www.interscience.wiley.com) DOI: 10.1002/path.2039 , 2006 .

[33]  N. Metreveli,et al.  Cardiomyocyte defects in diabetic models and protection with cardiac-targeted transgenes. , 2005, Methods in molecular medicine.

[34]  T. Penning,et al.  Structure-function of human 3 alpha-hydroxysteroid dehydrogenases: genes and proteins. , 2004, Molecular and cellular endocrinology.

[35]  L. Debelle,et al.  Predictions of the secondary structure and antigenicity of human and bovine tropoelastins , 2004, European Biophysics Journal.

[36]  N. Palackal,et al.  The reactive oxygen species--and Michael acceptor-inducible human aldo-keto reductase AKR1C1 reduces the alpha,beta-unsaturated aldehyde 4-hydroxy-2-nonenal to 1,4-dihydroxy-2-nonene. , 2001, The Journal of biological chemistry.

[37]  J. Gibrat,et al.  GOR method for predicting protein secondary structure from amino acid sequence. , 1996, Methods in enzymology.

[38]  H. Esterbauer,et al.  Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. , 1991, Free radical biology & medicine.

[39]  C. Fullmer,et al.  Amino acid sequence and comparative antigenicity of chicken metallothionein. , 1988, Proceedings of the National Academy of Sciences of the United States of America.