Expression and initial characterization of human ALDH3B1

Marchitti, Satori A.; Orlicky, David J.; Vasiliou, Vasilis

doi:10.1016/j.bbrc.2007.03.046

Cited by 45 publications

(59 citation statements)

References 31 publications

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“…Recent data suggest that this enzyme reacts with medium-and long-chain aliphatic aldehydes, potential products of fatty acids released by the droplet, and thereby protects the cell from oxidative stress ( 66 ).…”

Section: Two Other Enzymes Of Lipid Metabolism Of the Droplet Proteommentioning

confidence: 99%

Demonstrated and inferred metabolism associated with cytosolic lipid droplets

Goodman

2009

Journal of Lipid Research

102

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The next layer of complexity is the functional inhomogeneity of droplets. Subsets of droplets within the same cells exist with different populations of PAT proteins, differentiating among different sizes, ages, and levels of metabolic activity ( 3,4 ). Perhaps most surprisingly, droplets may be comprised, at least in some cases, not of the layered core-phospholipid shell architecture at all but a knot of tightly woven endoplasmic reticulum (ER) surrounded by secreted neutral lipid, itself encased with a single leaflet. Such a model is based on electron microscopic thin sections ( 5 ), freeze fracture-immunogold evidence ( 6 ), immunohistochemical studies of ER luminal proteins within the droplet ( 7 ), and the identifi cation of these proteins, notably ER chaperones, in several proteomic studies. Although certainly, such a complex structure must obey physical laws governing aqueous interactions with hydrophobic lipids and artifacts in processing for electron microscopy do occur, it may be best at present to keep an open mind and consider that droplets may not have the same structure among tissues and that they may take multiple physical forms in rapid order as they dynamically perform their functions.What are these functions? The most obvious one is lipid metabolism, namely the biogenesis and breakdown of the neutral lipids contained within the droplet. Although this conclusion predates proteomic studies ( 8 ), these recent studies have revealed the breadth and conservation of metabolic reactions that occur at or near the droplet surface, the subject of this review. Moreover, proteomics has demonstrated the surprising fact that droplets are likely to be very active in organellar communication because they are replete in rab proteins and other traffi cking molecules. Our knowledge from proteomic studies of droplet Abstract Cytosolic lipid droplets were considered until recently to be rather inert particles of stored neutral lipid. Largely through proteomics is it now known that droplets are dynamic organelles and that they participate in several important metabolic reactions as well as traffi cking and interorganellar communication. In this review, the role of droplets in metabolism in the yeast Saccharomyces cerevisiae , the fl y Drosophila melanogaster , and several mammalian sources are discussed, particularly focusing on those reactions shared by these organisms. From proteomics and older work, it is clear that droplets are important for fatty acid and sterol biosynthesis, fatty acid activation, and lipolysis. However, many droplet-associated enzymes are predicted to span a membrane two or more times, which suggests either that droplet structure is more complex than the current model posits, or that there are tightly bound membranes, particularly derived from the endoplasmic reticulum, which account for the association of several of these proteins. Cytosolic lipid droplets, originally thought to be simply coalesced neutral lipids waiting for lipolysis at metabolic demand, are now known to be considerably more...

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Section: Two Other Enzymes Of Lipid Metabolism Of the Droplet Proteommentioning

confidence: 99%

Demonstrated and inferred metabolism associated with cytosolic lipid droplets

Goodman

2009

Journal of Lipid Research

102

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“…ALDH3B1 is also expressed ubiquitously, and its protein levels are high in the kidney, liver, and ovary [15,16]. Similar to ALDH3A2, human ALDH3B1 exhibits activity toward medium-chain to long-chain aldehydes; in contrast to ALDH3A2, its subcellular localization is in the plasma membrane [17].…”

Section: Introductionmentioning

confidence: 99%

Mouse aldehyde dehydrogenase ALDH3B2 is localized to lipid droplets via two C-terminal tryptophan residues and lipid modification

Kitamura

Takagi

Naganuma

et al. 2014

Biochemical Journal

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Short title: Lipid droplet localization of ALDH3B2Summary statement: The mouse aldehyde dehydrogenases ALDH3B2 and ALDH3B3 exhibit similar substrate specificity but distinct intracellular localization (ALDH3B2, lipid droplets; ALDH3B3, plasma membrane). The C-terminal prenylation and two Trp residues are important for the lipid droplet localization of ALDH3B2.2 ABSTRACT Aldehyde dehydrogenases (ALDHs) catalyze the conversion of toxic aldehydes to non-toxic carboxylic acids. Of the 21 ALDHs in mice, it is the ALDH3 family members (ALDH3A1, ALDH3A2, ALDH3B1, ALDH3B2, and ALDH3B3) that are responsible for the removal of lipid-derived aldehydes. However, ALDH3B2 and ALDH3B3 have yet to be characterized.Here, we examined the enzyme activity, tissue distribution, and subcellular localization of ALDH3B2 and ALDH3B3. Both were found to exhibit broad substrate preferences from medium-chain to long-chain aldehydes, resembling ALDH3A2 and ALDH3B1. Although ALDH3B2 and ALDH3B3 share extremely high sequence similarity, their localizations differed, with ALDH3B2 found in lipid droplets and ALDH3B3 localized to the plasma membrane. Both ALDH3B2 and ALDH3B3 were modified by prenylation at their C-termini; this modification greatly influenced their membrane localization and enzymatic activity toward hexadecanal. We found that their C-terminal regions, particularly the two Trp residues (Trp462 and Trp469) of ALDH3B2 and the two Arg residues (Arg462 and Arg463) of ALDH3B3, were important for the determination of their specific localization. Abnormal quantity and perhaps quality of lipid droplets are implicated in several metabolic diseases. We speculate that ALDH3B2 acts to remove lipid-derived aldehydes in lipid droplets generated via oxidative stress as a quality control mechanism.

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“…In addition, stable expression of ALDH3B1 protects cultured cells from cytotoxicity induced by LPO-derived aldehydes. As such, we postulate that ALDH3B1, similar to other members of the ALDH3 family (Pappa et al 2003), plays an important physiological role against cellular oxidative stress by detoxifying aldehydes derived from oxidative processes, such as ethanol metabolism and LPO (Marchitti et al 2007b).…”

Section: Introductionmentioning

confidence: 99%

“…Using Western blot analyses, we previously have shown that an ALDH3B1 85% similar to the human enzyme is expressed in various mouse tissues, including kidney, liver, lung, and regions of the brain (Marchitti et al 2007b). However, IHC permits cellular (and subcellular) protein expression to be identified; therefore, it can be used to further elucidate the potential physiological roles and significance of proteins in human tissues.…”

Section: Introductionmentioning

confidence: 99%

“…We have previously shown that ALDH3B1 is a metabolically active enzyme with distinct specificity for various aldehyde substrates, particularly medium-and long-chain aliphatic aldehydes. These substrates include many products that are formed during LPO, such as hexanal, 4-hydroxy-2-nonenal (4-HNE), octanal, and trans-2-nonenal (Marchitti et al 2007b). In addition, stable expression of ALDH3B1 protects cultured cells from cytotoxicity induced by LPO-derived aldehydes.…”

Section: Introductionmentioning

confidence: 99%

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

Marchitti

Orlicky

Brocker

et al. 2010

J Histochem Cytochem.

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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)

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Expression and initial characterization of human ALDH3B1

Cited by 45 publications

References 31 publications

Demonstrated and inferred metabolism associated with cytosolic lipid droplets

Demonstrated and inferred metabolism associated with cytosolic lipid droplets

Mouse aldehyde dehydrogenase ALDH3B2 is localized to lipid droplets via two C-terminal tryptophan residues and lipid modification

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

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