198
Y. Shen et al. / Chemico-Biological Interactions 191 (2011) 192–198
this study than that reported previously. In this study, the mild sul-
phydryl reducer, -ME (10 mM) was used in protein preparation,
but dithiothreitol-reduction of 1B1 was not conducted before the
enzyme activity assay in order to make the in vitro data more sim-
ilar to physiological conditions. Indeed, this enzymatic data fitted
well with that from the intracellular study. In 293T cells, ectopi-
cally expressed EGFP-AKR1B10 efficiently converted HNE at 5 M
to DHN, but the endogenously expressed 1B1, although active to
d,l-glyceraldehyde, did not. As a result, DHN was barely detectable
in the vector control 293T cells. In this study, serum-free cell sus-
pensions were used to exclude serum-derived artifacts that may
affect HNE metabolism.
AKR1B10 is highly induced in human tumors [12,13]. The find-
role of 1B10 in cancer development and progression. Cancer cells
grow aggressively and are metabolically active, thus having a high
burden of toxic carbonyl compounds. 1B10 upregulated in cancer
cells may facilitate the cell growth and proliferation via eliminating
the toxic carbonyl compounds [33,37].
[11] R. Tammali, A.B. Reddy, K.V. Ramana, J.M. Petrash, S.K. Srivastava, Aldose reduc-
tase deficiency in mice prevents azoxymethane-induced colonic preneoplastic
aberrant crypt foci formation, Carcinogenesis 30 (5) (2009) 799–807.
[12] D. Cao, S.T. Fan, S.S. Chung, Identification and characterization of a novel human
aldose reductase-like gene, J. Biol. Chem. 273 (19) (1998) 11429–11435.
[13] S. Chung, J. LaMendola, Cloning and sequence determination of human placen-
tal aldose reductase gene, J. Biol. Chem. 264 (25) (1989) 14775–14777.
[14] D.J. Hyndman, T.G. Flynn, Sequence and expression levels in human tissues of
a new member of the aldo–keto reductase family, Biochim. Biophys. Acta 1399
(2–3) (1998) 198–202.
[15] G. Aldini, I. Dalle-Donne, R.M. Facino, A. Milzani, M. Carini, Intervention
strategies to inhibit protein carbonylation by lipoxidation-derived reactive
carbonyls, Med. Res. Rev. 27 (6) (2007) 817–868.
[16] L. Zhong, Z. Liu, R. Yan, S. Johnson, Y. Zhao, X. Fang, D. Cao, Aldo–keto
reductase family 1 B10 protein detoxifies dietary and lipid-derived alpha, beta-
unsaturated carbonyls at physiological levels, Biochem. Biophys. Res. Commun.
387 (2) (2009) 245–250.
[17] M. Spite, S.P. Baba, Y. Ahmed, O.A. Barski, K. Nijhawan, J.M. Petrash, A. Bhat-
nagar, S. Srivastava, Substrate specificity and catalytic efficiency of aldo–keto
reductases with phospholipid aldehydes, Biochem. J. 405 (1) (2007) 95–105.
[18] H.J. Martin, E. Maser, Role of human aldo–keto-reductase AKR1B10 in the pro-
tection against toxic aldehydes, Chem. Biol. Interact. 178 (1–3) (2009) 145–150.
[19] F.X. Ruiz, O. Gallego, A. Ardevol, A. Moro, M. Dominguez, S. Alvarez, R. Alvarez,
A.R. de Lera, C. Rovira, I. Fita, X. Pares, J. Farres, Aldo–keto reductases from the
AKR1B subfamily: retinoid specificity and control of cellular retinoic acid levels,
Chem. Biol. Interact. 178 (1–3) (2009) 171–177.
[20] O. Gallego, F.X. Ruiz, A. Ardevol, M. Dominguez, R. Alvarez, A.R. de Lera, C. Rovira,
J. Farres, I. Fita, X. Pares, Structural basis for the high all-trans-retinaldehyde
reductase activity of the tumor marker AKR1B10, Proc. Natl. Acad. Sci. U.S.A.
104 (52) (2007) 20764–20769.
In summary, 1B1 and 1B10 are both expressed in the human
GI tract, but have differential substrate specificity on free or GS-
conjugated carbonyl compounds, suggesting their distinct roles
against carbonyl lesions.
[21] A.M. Quinn, R.G. Harvey, T.M. Penning, Oxidation of PAH trans-dihydrodiols
by human aldo–keto reductase AKR1B10, Chem. Res. Toxicol. 21 (11) (2008)
2207–2215.
[22] H.J. Martin, U. Breyer-Pfaff, V. Wsol, S. Venz, S. Block, E. Maser, Purification and
characterization of akr1b10 from human liver: role in carbonyl reduction of
xenobiotics, Drug Metab. Dispos. 34 (3) (2006) 464–470.
Conflict of interest
There is no potential conflict of interest in this study.
[23] G.K. Balendiran, H.J. Martin, Y. El-Hawari, E. Maser, Cancer biomarker AKR1B10
and carbonyl metabolism, Chem. Biol. Interact. 178 (1–3) (2009) 134–137.
[24] G.K. Balendiran, Fibrates in the chemical action of daunorubicin, Curr. Cancer
Drug Targets 9 (3) (2009) 366–369.
Acknowledgements
[25] R. De Bont, N. van Larebeke, Endogenous DNA damage in humans: a review of
quantitative data, Mutagenesis 19 (3) (2004) 169–185.
This work was supported in part by National Cancer Institute
(CA122622) and Department of Defense Breast Cancer Research
Program (BC083555). Yi Shen was supported by USPHS NIH grant
R13-AA019612 to present this work at the 15th International Meet-
ing on Enzymology and Molecular Biology of Carbonyl Metabolism
in Lexington, KY, USA.
[26] V.V. Davydov, N.M. Dobaeva, A.I. Bozhkov, Possible role of alteration of alde-
hyde’s scavenger enzymes during aging, Exp. Gerontol. 39 (1) (2004) 11–16.
[27] K. Berhane, M. Widersten, A. Engstrom, J.W. Kozarich, B. Mannervik, Detoxi-
cation of base propenals and other alpha, beta-unsaturated aldehyde products
of radical reactions and lipid peroxidation by human glutathione transferases,
Proc. Natl. Acad. Sci. U.S.A. 91 (4) (1994) 1480–1484.
[28] H. Esterbauer, P. Eckl, A. Ortner, Possible mutagens derived from lipids and lipid
precursors, Mutat. Res. 238 (3) (1990) 223–233.
Appendix A. Supplementary data
[29] G.W. Wang, Y. Guo, T.M. Vondriska, J. Zhang, S. Zhang, L.L. Tsai, N.C. Zong, R.
Bolli, A. Bhatnagar, S.D. Prabhu, Acrolein consumption exacerbates myocar-
dial ischemic injury and blocks nitric oxide-induced PKCepsilon signaling and
cardioprotection, J. Mol. Cell. Cardiol. 44 (6) (2008) 1016–1022.
[30] B.D. Schuler, E. Eder, Development of a 32P-postlabelling method for the detec-
tion of 1,N2-propanodeoxyguanosine adducts of crotonaldehyde in vivo, Arch.
Toxicol. 74 (7) (2000) 404–414.
Supplementary data associated with this article can be found, in
References
[31] M.D. Stout, E. Bodes, R. Schoonhoven, P.B. Upton, G.S. Travlos, J.A. Swen-
berg, Toxicity, DNA binding, and cell proliferation in male F344 rats following
short-term gavage exposures to trans-2-hexenal, Toxicol. Pathol. 36 (2) (2008)
232–246.
[32] S. Srivastava, S.J. Watowich, J.M. Petrash, S.K. Srivastava, A. Bhatnagar, Struc-
tural and kinetic determinants of aldehyde reduction by aldose reductase,
Biochemistry 38 (1) (1999) 42–54.
[33] X. Zu, R. Yan, S. Robbins, P.A. Krishack, D.F. Liao, D. Cao, Reduced 293T cell
susceptibility to acrolein due to aldose reductase-like-1 protein expression,
Toxicol. Sci. 97 (2) (2007) 562–568.
[34] J.Z. Cheng, R. Sharma, Y. Yang, S.S. Singhal, A. Sharma, M.K. Saini, S.V. Singh, P.
Zimniak, S. Awasthi, Y.C. Awasthi, Accelerated metabolism and exclusion of 4-
hydroxynonenal through induction of RLIP76 and hGST5.8 is an early adaptive
response of cells to heat and oxidative stress, J. Biol. Chem. 276 (44) (2001)
41213–41223.
[35] B.F. Coles, F.F. Kadlubar, Detoxification of electrophilic compounds by glu-
tathione S-transferase catalysis: determinants of individual response to
chemical carcinogens and chemotherapeutic drugs? BioFactors (Oxford, Eng-
land) 17 (1–4) (2003) 115–130.
[36] S. Srivastava, A. Chandra, A. Bhatnagar, S.K. Srivastava, N.H. Ansari, Lipid perox-
idation product, 4-hydroxynonenal and its conjugate with GSH are excellent
substrates of bovine lens aldose reductase, Biochem. Biophys. Res. Commun.
217 (3) (1995) 741–746.
[37] R. Yan, X. Zu, J. Ma, Z. Liu, M. Adeyanju, D. Cao, Aldo–keto reductase family
1 B10 gene silencing results in growth inhibition of colorectal cancer cells:
implication for cancer intervention, Int. J. Cancer 121 (10) (2007) 2301–2306.
[38] Y. Shen, L. Zhong, S. Markwell, D. Cao, Thiol-disulfide exchanges modulate
aldo–keto reductase family 1 member B10 activity and sensitivity to inhibitors,
Biochimie 92 (5) (2010) 530–537.
[1] R.D. Mindnich, T.M. Penning, Aldo–keto reductase (AKR) superfamily:
genomics and annotation, Hum. Genomics 3 (4) (2009) 362–370.
[2] J.M. Jez, T.G. Flynn, T.M. Penning, A new nomenclature for the aldo–keto reduc-
tase superfamily, Biochem. Pharmacol. 54 (6) (1997) 639–647.
[3] O.A. Barski, S.M. Tipparaju, A. Bhatnagar, The aldo–keto reductase superfamily
and its role in drug metabolism and detoxification, Drug Metab. Rev. 40 (4)
(2008) 553–624.
[4] J.M. Petrash, All in the family: aldose reductase and closely related aldo–keto
reductases, Cell. Mol. Life Sci. 61 (7–8) (2004) 737–749.
[5] Y. Jin, T.M. Penning, Aldo–keto reductases and bioactivation/detoxication,
Annu. Rev. Pharmacol. Toxicol. 47 (2007) 263–292.
[6] N. Yasuda, K. Fujino, T. Shiraji, F. Nambu, K. Kondo, Effects of steroid 5alpha-
reductase inhibitor ONO-9302 and anti-androgen allylestrenol on the prostatic
growth, and plasma and prostatic hormone levels in rats, Jpn. J. Pharmacol. 74
(3) (1997) 243–252.
[7] J. Jin, P.A. Krishack, D. Cao, Role of aldo–keto reductases in development of
prostate and breast cancer, Front. Biosci. 11 (2006) 2767–2773.
[8] K.W. Lee, B.C. Ko, Z. Jiang, D. Cao, S.S. Chung, Overexpression of aldose reductase
in liver cancers may contribute to drug resistance, Anticancer Drugs 12 (2)
(2001) 129–132.
[9] C. Wang, R. Yan, D. Luo, K. Watabe, D.F. Liao, D. Cao, Aldo–keto reductase fam-
ily 1 member B10 promotes cell survival by regulating lipid synthesis and
eliminating carbonyls, J. Biol. Chem. 284 (39) (2009) 26742–26748.
[10] J. Ma, R. Yan, X. Zu, J.M. Cheng, K. Rao, D.F. Liao, D. Cao, Aldo–keto reductase
family 1 B10 affects fatty acid synthesis by regulating the stability of acetyl-
CoA carboxylase-alpha in breast cancer cells, J. Biol. Chem. 283 (6) (2008)
3418–3423.