T he aldo-keto reductase (AKR) superfamily includes a group of monomeric 37-kDa soluble reduced nicotinamide adenine dinucleotide phosphate-dependent oxidoreductases that function in elimination reactions by modifying carbonyl groups on aldehyde or ketones to form primary or secondary alcohols, which are then conjugated with sulfates or glucuronide for excretion. [1][2][3][4][5][6] Like the cytochrome P450 superfamily, the AKRs are classifi ed as a phase 1 drug, xenobiotic and carcinogen-metabolizing enzymes. 7 One of the Smoking-Induced Upregulation of AKR1B10 Expression in the Airway Epithelium of Healthy IndividualsRui Wang , MD , PhD ; Guoqing Wang , PhD ; Megan J. Ricard , MS ; Barbara Ferris , BA ; Yael Strulovici-Barel , MSc ; Jacqueline Salit , MS ; Neil R. Hackett , PhD ; Lorraine J. Gudas , PhD ; and Ronald G. Crystal Background: The aldo-keto reductase (AKR) gene superfamily codes for monomeric, soluble reduced nicotinamide adenine dinucleotide phosphate-dependent oxidoreductases that mediate elimination reactions. AKR1B10, an AKR that eliminates retinals, has been observed as upregulated in squamous metaplasia and non-small cell lung cancer and has been suggested as a diagnostic marker specifi c to tobacco-related carcinogenesis. We hypothesized that upregulation of AKR1B10 expression may be initiated in healthy smokers prior to the development of evidence of lung cancer. Methods: Expression of AKR1B10 was assessed at the mRNA level using microarrays with TaqMan confi rmation in the large airway epithelium (21 healthy nonsmokers, 31 healthy smokers) and small airway epithelium (51 healthy nonsmokers, 58 healthy smokers) obtained by fi beroptic bronchoscopy and brushing. Results: Compared with healthy nonsmokers, AKR1B10 mRNA levels were signifi cantly upregulated in both large and small airway epithelia of healthy smokers. Consistent with the mRNA data, AKR1B10 protein was signifi cantly upregulated in the airway epithelium of healthy smokers as assessed by Western blot analysis and immunohistochemistry, with AKR1B10 expressed in both differentiated and basal cells. Finally, cigarette smoke extract mediated upregulation of AKR1B10 in airway epithelial cells in vitro, and transfection of AKR1B10 into airway epithelial cells enhanced the conversion of retinal to retinol. Conclusions: Smoking per se mediates upregulation of AKR1B10 expression in the airway epithelia of healthy smokers with no evidence of lung cancer. In the context of these observations and the link of AKR1B10 to the metabolism of retinals and to lung cancer, the smoking-induced upregulation of AKR1B10 may be an early process in the multiple events leading to lung cancer.

Background: How to differentiate embryonic stem cells into specific neuronal types is a key question. Results: Lack of Cyp26a1 results in increased ALDH1a2 and Hoxc6, markers of lateral motor column identity. Conclusion:The cytochrome P450 enzyme Cyp26a1 plays a critical role in specifying motor neuron columnar subtypes. Significance: Blocking Cyp26a1 has therapeutic potential in regenerative medicine, neurodegenerative diseases, and cancer therapies.