Aldehyde Dehydrogenases in Cellular Responses to Oxidative/electrophilic Stress

doi:10.1016/J.FREERADBIOMED.2012.11.010

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Aldehyde Dehydrogenases in Cellular Responses to Oxidative/electrophilic Stress

Journal Article•DOI•

Aldehyde Dehydrogenases in Cellular Responses to Oxidative/electrophilic Stress

Surendra Singh¹, Chad Brocker¹, Vindhya Koppaka¹, Ying Chen¹, Brian C. Jackson¹, Akiko Matsumoto², David C. Thompson¹, Vasilis Vasiliou¹ - Show less +4 more•Institutions (2)

University of Montana¹, Saga University²

01 Mar 2013-Free Radical Biology and Medicine (NIH Public Access)-Vol. 56, pp 89-101

TL;DR: The ALDH superfamily represents a fundamentally important class of enzymes that contributes significantly to the management of electrophilic/oxidative stress within living systems and is associated with a variety of pathological conditions in humans.

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About: This article is published in Free Radical Biology and Medicine.The article was published on 2013-03-01 and is currently open access. It has received 450 citations till now. The article focuses on the topics: Oxidative stress & Aldehyde dehydrogenase.

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Journal Article•DOI•

Targeting cancer stem cell pathways for cancer therapy

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Liqun Yang¹, Pengfei Shi¹, Gaichao Zhao¹, Jie Xu¹, Wen Peng¹, Jiayi Zhang¹, Guanghui Zhang¹, Xiaowen Wang¹, Zhen Dong¹, Fei Chen², Hongjuan Cui¹ - Show less +7 more•Institutions (2)

Southwest University¹, Eugene Applebaum College of Pharmacy and Health Sciences²

07 Feb 2020-Signal Transduction and Targeted Therapy

TL;DR: Molecules, vaccines, antibodies, and CAR-T (chimeric antigen receptor T cell) cells have been developed to specifically target CSCs, and some of these factors are already undergoing clinical trials.

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Abstract: Since cancer stem cells (CSCs) were first identified in leukemia in 1994, they have been considered promising therapeutic targets for cancer therapy. These cells have self-renewal capacity and differentiation potential and contribute to multiple tumor malignancies, such as recurrence, metastasis, heterogeneity, multidrug resistance, and radiation resistance. The biological activities of CSCs are regulated by several pluripotent transcription factors, such as OCT4, Sox2, Nanog, KLF4, and MYC. In addition, many intracellular signaling pathways, such as Wnt, NF-κB (nuclear factor-κB), Notch, Hedgehog, JAK-STAT (Janus kinase/signal transducers and activators of transcription), PI3K/AKT/mTOR (phosphoinositide 3-kinase/AKT/mammalian target of rapamycin), TGF (transforming growth factor)/SMAD, and PPAR (peroxisome proliferator-activated receptor), as well as extracellular factors, such as vascular niches, hypoxia, tumor-associated macrophages, cancer-associated fibroblasts, cancer-associated mesenchymal stem cells, extracellular matrix, and exosomes, have been shown to be very important regulators of CSCs. Molecules, vaccines, antibodies, and CAR-T (chimeric antigen receptor T cell) cells have been developed to specifically target CSCs, and some of these factors are already undergoing clinical trials. This review summarizes the characterization and identification of CSCs, depicts major factors and pathways that regulate CSC development, and discusses potential targeted therapy for CSCs.

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787 citations

Cites background from "Aldehyde Dehydrogenases in Cellular..."

...According to previous studies, aldehyde dehydrogenase (ALDH), a marker in many CSCs,(34) eliminates oxidative stress and enhances resistance to chemotherapeutic drugs, such as oxazolidine, taxanes, and platinum drugs.(35) ALDH also removes free radicals induced by radiation and stimulates resistance to radiation....
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...ALDH also removes free radicals induced by radiation and stimulates resistance to radiation.(35) Inducing DNA damage and apoptosis through chemotherapy and radiotherapy are commonly used cancer treatments....
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Journal Article•DOI•

A role for cancer stem cells in therapy resistance: cellular and molecular mechanisms.

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Monica Cojoc¹, Katrin Mäbert¹, Michael H. Muders², Anna Dubrovska³, Anna Dubrovska¹ - Show less +1 more•Institutions (3)

Helmholtz-Zentrum Dresden-Rossendorf¹, Dresden University of Technology², German Cancer Research Center³

01 Apr 2015-Seminars in Cancer Biology

TL;DR: The mechanisms of CSC-related therapy resistance including drug efflux by ABC transporters, activation of aldehyde dehydrogenase and developmental pathways, enhanced DNA damage response, autophagy and microenvironmental conditions are described, and possible therapeutic strategies for improving cancer treatment are discussed.

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334 citations

Journal Article•DOI•

The cancer stem cell marker aldehyde dehydrogenase is required to maintain a drug-tolerant tumor cell subpopulation

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Debasish Raha, Timothy R. Wilson, Jing Peng, David A. Peterson, Peng Yue¹, Marie Evangelista, Catherine Wilson, Mark Merchant, Jeff Settleman - Show less +5 more•Institutions (1)

Genentech¹

08 May 2014-Cancer Research

TL;DR: It is found that ALDH protects the drug-tolerant subpopulation from the potentially toxic effects of elevated levels of reactive oxygen species (ROS) in these cells, and pharmacologic disruption of ALDH activity leads to accumulation of ROS to toxic levels, consequent DNA damage, and apoptosis specifically within the drug.

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Abstract: Selective kinase inhibitors have emerged as an important class of cancer therapeutics, and several such drugs are now routinely used to treat advanced-stage disease. However, their clinical benefit is typically short-lived because of the relatively rapid acquisition of drug resistance following treatment response. Accumulating preclinical and clinical data point to a role for a heterogeneous response to treatment within a subpopulation of tumor cells that are intrinsically drug-resistant, such as cancer stem cells. We have previously described an epigenetically determined reversibly drug-tolerant subpopulation of cancer cells that share some properties with cancer stem cells. Here, we define a requirement for the previously established cancer stem cell marker ALDH (aldehyde dehydrogenase) in the maintenance of this drug-tolerant subpopulation. We find that ALDH protects the drug-tolerant subpopulation from the potentially toxic effects of elevated levels of reactive oxygen species (ROS) in these cells, and pharmacologic disruption of ALDH activity leads to accumulation of ROS to toxic levels, consequent DNA damage, and apoptosis specifically within the drug-tolerant subpopulation. Combining ALDH inhibition with other kinase-directed treatments delayed treatment relapse in vitro and in vivo, revealing a novel combination treatment strategy for cancers that might otherwise rapidly relapse following single-agent therapy.

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238 citations

Journal Article•DOI•

Aldehyde Dehydrogenases: Not Just Markers, but Functional Regulators of Stem Cells.

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Giuseppe Vassalli

13 Jan 2019-Stem Cells International

TL;DR: Mounting evidence suggests that ALDH not only may be used as a marker for stem cells but also may well regulate cellular functions related to self-renewal, expansion, differentiation, and resistance to drugs and radiation.

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Abstract: Aldehyde dehydrogenase (ALDH) is a superfamily of enzymes that detoxify a variety of endogenous and exogenous aldehydes and are required for the biosynthesis of retinoic acid (RA) and other molecular regulators of cellular function. Over the past decade, high ALDH activity has been increasingly used as a selectable marker for normal cell populations enriched in stem and progenitor cells, as well as for cell populations from cancer tissues enriched in tumor-initiating stem-like cells. Mounting evidence suggests that ALDH not only may be used as a marker for stem cells but also may well regulate cellular functions related to self-renewal, expansion, differentiation, and resistance to drugs and radiation. ALDH exerts its functional actions partly through RA biosynthesis, as all-trans RA reverses the functional effects of pharmacological inhibition or genetic suppression of ALDH activity in many cell types in vitro. There is substantial evidence to suggest that the role of ALDH as a stem cell marker comes down to the specific isoform(s) expressed in a particular tissue. Much emphasis has been placed on the ALDH1A1 and ALDH1A3 members of the ALDH1 family of cytosolic enzymes required for RA biosynthesis. ALDH1A1 and ALDH1A3 regulate cellular function in both normal stem cells and tumor-initiating stem-like cells, promoting tumor growth and resistance to drugs and radiation. An improved understanding of the molecular mechanisms by which ALDH regulates cellular function will likely open new avenues in many fields, especially in tissue regeneration and oncology.

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204 citations

Cites background from "Aldehyde Dehydrogenases in Cellular..."

...By metabolizing a wide range of aldehydes, ALDH can attenuate oxidative stress [14]....
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...ALDH upregulation occurs in bacteria in response to environmental and chemical stressors; in plants in response to dehydration, salinity, and oxidative stress; in yeasts after exposure to ethanol and oxidative stress; and in mammals in response to oxidative stress and lipid peroxidation [14]....
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...The underlying mechanism is incompletely understood, but RA biosynthesis and scavenging of reactive oxygen species (ROS) and toxic aldehydes are likely involved [14, 20, 116]....
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Journal Article•DOI•

Varieties, production, composition and health benefits of vinegars: A review.

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Chin Wai Ho¹, Azwan Mat Lazim¹, Shazrul Fazry¹, Umi Kalsum Hj Hussain Zaki², Seng Joe Lim¹ - Show less +1 more•Institutions (2)

National University of Malaysia¹, Malaysian Agricultural Research and Development Institute²

15 Apr 2017-Food Chemistry

TL;DR: The main volatile compound in vinegar is acetic acid, which gives vinegar its strong, sour aroma and flavour, and other volatile compounds present in vinegars are mainly alcohols, acids, esters, aldehydes and ketones.

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190 citations

Cites background from "Aldehyde Dehydrogenases in Cellular..."

...AlDH metabolises electrophilic aldehydes and can be expressed in all forms of life from simple to complex multicellular organisms (Singh et al., 2013)....
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...According to Singh et al. (2013), the elevation of AlDH protects against oxidative damage....
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References

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Open Access

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6,456 citations

"Aldehyde Dehydrogenases in Cellular..." refers background in this paper

...Several ALDHs are also involved in the detoxification of LPO-derived reactive aldehydes, which are implicated in promoting covalent modification of proteins and DNA and in diseases resulting from such modifications [38,39]....
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...Oxidative stress initiates LPO and yields reactive aldehydes, such as 4-HNE, which induce covalent modification of proteins and DNA [38]....
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Journal Article•DOI•

ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome.

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Christophe Ginestier¹, Min Hee Hur², Emmanuelle Charafe-Jauffret³, Florence Monville³, Julie Dutcher¹, Marty Brown¹, Jocelyne Jacquemier³, Patrice Viens³, Celina G. Kleer¹, Suling Liu¹, Anne F. Schott¹, Daniel F. Hayes¹, Daniel Birnbaum³, Max S. Wicha¹, Gabriela Dontu¹ - Show less +11 more•Institutions (3)

University of Michigan¹, Sungkyunkwan University², French Institute of Health and Medical Research³

15 Nov 2007-Cell Stem Cell

TL;DR: It is shown that normal and cancer human mammary epithelial cells with increased aldehyde dehydrogenase activity (ALDH) have stem/progenitor properties and these cells contain the subpopulation of normal breast epithelium with the broadest lineage differentiation potential and greatest growth capacity in a xenotransplant model.

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3,766 citations

"Aldehyde Dehydrogenases in Cellular..." refers background in this paper

...Recently, however, the activity of other ALDH isozymes, including ALDH1A2, ALDH1A3, ALDH1A7, ALDH2, ALDH3A1, ALDH4A1, ALDH5A1, ALDH6, and ALDH9A1, has been shown to contribute to the elevated ALDH activity observed in cancer stem cells [150,151]....
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Journal Article•DOI•

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"Aldehyde Dehydrogenases in Cellular..." refers background in this paper

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Journal Article•DOI•

Biochemistry and pathology of radical-mediated protein oxidation

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Roger T. Dean¹, Shanlin Fu¹, Roland Stocker¹, Michael J. Davies¹•Institutions (1)

The Heart Research Institute¹

15 May 1997-Biochemical Journal

TL;DR: Proteins are also key targets in defensive cytolysis and in inflammatory self-damage, and the possibility of selective protection against protein oxidation (antioxidation) is raised.

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Abstract: Radical-mediated damage to proteins may be initiated by electron leakage, metal-ion-dependent reactions and autoxidation of lipids and sugars. The consequent protein oxidation is O2-dependent, and involves several propagating radicals, notably alkoxyl radicals. Its products include several categories of reactive species, and a range of stable products whose chemistry is currently being elucidated. Among the reactive products, protein hydroperoxides can generate further radical fluxes on reaction with transition-metal ions; protein-bound reductants (notably dopa) can reduce transition-metal ions and thereby facilitate their reaction with hydroperoxides; and aldehydes may participate in Schiff-base formation and other reactions. Cells can detoxify some of the reactive species, e.g. by reducing protein hydroperoxides to unreactive hydroxides. Oxidized proteins are often functionally inactive and their unfolding is associated with enhanced susceptibility to proteinases. Thus cells can generally remove oxidized proteins by proteolysis. However, certain oxidized proteins are poorly handled by cells, and together with possible alterations in the rate of production of oxidized proteins, this may contribute to the observed accumulation and damaging actions of oxidized proteins during aging and in pathologies such as diabetes, atherosclerosis and neurodegenerative diseases. Protein oxidation may also sometimes play controlling roles in cellular remodelling and cell growth. Proteins are also key targets in defensive cytolysis and in inflammatory self-damage. The possibility of selective protection against protein oxidation (antioxidation) is raised.

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1,649 citations

"Aldehyde Dehydrogenases in Cellular..." refers background in this paper

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Journal Article•DOI•

Oxidative stress in bacteria and protein damage by reactive oxygen species.

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Elisa Cabiscol¹, Jordi Tamarit, Joaquim Ros•Institutions (1)

University of Lleida¹

01 Mar 2000-International Microbiology

TL;DR: This paper reviews major key points in the generation of reactive oxygen species in bacteria, defense mechanisms and genetic responses to oxidative stress, with special attention to oxidative damage to proteins.

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Abstract: The advent of O2 in the atmosphere was among the first major pollution events occurred on earth. The reaction between ferrous iron, very abundant in the reductive early atmosphere, and oxygen results in the formation of harmful superoxide and hydroxyl radicals, which affect all macromolecules (DNA, lipids and proteins). Living organisms have to build up mechanisms to protect themselves against oxidative stress, with enzymes such as catalase and superoxide dismutase, small proteins like thioredoxin and glutaredoxin, and molecules such as glutathione. Bacterial genetic responses to oxidative stress are controlled by two major transcriptional regulators (OxyR and SoxRS). This paper reviews major key points in the generation of reactive oxygen species in bacteria, defense mechanisms and genetic responses to oxidative stress. Special attention is paid to the oxidative damage to proteins.

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1,384 citations

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