Aldehyde Dehydrogenase 3B1 (ALDH3B1): Immunohistochemical Tissue Distribution and Cellular-specific Localization in Normal and Cancerous Human Tissues

Abstract

S U M M A R Y Aldehyde dehydrogenase (ALDH) enzymes are critical in the detoxification of endogenous and exogenous aldehydes. Our previous findings indicate that the ALDH3B1 enzyme is expressed in several mouse tissues and is catalytically active toward aldehydes derived from lipid peroxidation, suggesting a potential role against oxidative stress. The aim of this study was to elucidate by immunohistochemistry the tissue, cellular, and subcellular distribution of ALDH3B1 in normal human tissues and in tumors of human lung, colon, breast, and ovary. Our results indicate that ALDH3B1 is expressed in a tissue-specific manner and in a limited number of cell types, including hepatocytes, proximal convoluted tubule cells, cerebellar astrocytes, bronchiole ciliated cells, testis efferent ductule ciliated cells, and histiocytes. ALDH3B1 expression was upregulated in a high percentage of human tumors (lung . breast 5 ovarian . colon). Increased ALDH3B1 expression in tumor cells may confer a growth advantage or be the result of an induction mechanism mediated by increased oxidative stress. Subcellular localization of ALDH3B1 was predominantly cytosolic in tissues, with the exception of normal human lung and testis, in which localization appeared membrane-bound or membrane-associated. The specificity of ALDH3B1 distribution may prove to be directly related to the functional role of this enzyme in human tissues. (J Histochem Cytochem 58:765-783, 2010)

Substrate specificity, plasma membrane localization, and lipid modification of the aldehyde dehydrogenase ALDH3B1

“…ALDH3B1 is expressed in the kidney, liver, and brain and has been shown active in vitro toward C6 to C9 aldehydes [12]; however, its activity toward ≥C10 aldehydes is currently unknown. In addition, although ALDH3B1 is suggested to be localized in the plasma membrane and cytosol [13,14], the precise intracellular localization still remains to be elucidated. Unlike other ALDH3 family members, ALDH3B2 has so far not been well characterized.…”

Large Scale Statistical Analysis of GEO Datasets

“…Conversely, among the most significant genes for lung tumor, the following were found in C2 genesets related to lung and not in those related to breast: ALDH3B1, DARS, PRPSAP2, FAM96B, MBIP, LRRC20. The overexpression of ALDH3B1 in lung tumors has been reported in [49]. Santarius et al [50] gives lists of genes, the overexpression of which is associated to different types of human cancers.…”

Molecular Biology of Lung Cancer and Future Perspectives for Screening

“…A recent meta-analysis showed that increased ALDH1A1 expression is associated with poor OS and disease-free survival in lung cancer patients [35]. Previous studies showed that also several other ALDH isoforms are involved in lung cancer as ALDH3A1, highly expressed in two types of NSCLC, Ade and SCC, and ALDH3B1 expression was also found to be upregulated in a high percentage of human tumors, particularly in lung cancer [36][37][38].…”