Generation of Adducts of 4-Hydroxy-2-nonenal with Heat Shock 60 kDa Protein 1 in Human Promyelocytic HL-60 and Monocytic THP-1 Cell Lines

Arcaro, Alessia; Daga, Martina; Cetrangolo, Giovanni Paolo; Ciamporcero, Eric; Lepore, Alessio; Pizzimenti, Stefania; Petrella, Claudia; Graf, Maria; Uchida, Koji; Mamone, Gianfranco; Ferranti, Pasquale; Palumbo, Giuseppe; Barrera, Giuseppina; Gentile, Fabrizio

doi:10.1155/2015/296146

Cited by 11 publications

(12 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Collapsing of ∆Ψ is generally associated with fragmentation of the mitochondrial network [12]. In order to better substantiate mitochondrial damage, we assessed protein levels of HSP60 and MFN2, which represent molecular markers of mitochondrial stress [13][14][15] and dynamics (fission/fusion), respectively ( Figure 5C). Western blot analysis revealed that under resting conditions, the levels of Hsp60 in TM SSADH cells were greater with respect to control and WT SSADH cells and were maintained at high levels upon PQ treatment.…”

Section: Tm Ssadh Affects Mitochondrial Function and Increases Suscepmentioning

confidence: 99%

SSADH Variants Increase Susceptibility of U87 Cells to Mitochondrial Pro-Oxidant Insult

Menduti

Vitaliti

Capo

et al. 2020

IJMS

View full text Add to dashboard Cite

Succinate semialdehyde dehydrogenase (SSADH) is a mitochondrial enzyme, encoded by ALDH5A1, mainly involved in γ-aminobutyric acid (GABA) catabolism and energy supply of neuronal cells, possibly contributing to antioxidant defense. This study aimed to further investigate the antioxidant role of SSADH, and to verify if common SNPs of ALDH5A1 may affect SSADH activity, stability, and mitochondrial function. In this study, we used U87 glioblastoma cells as they represent a glial cell line. These cells were transiently transfected with a cDNA construct simultaneously harboring three SNPs encoding for a triple mutant (TM) SSADH protein (p.G36R/p.H180Y/p.P182L) or with wild type (WT) cDNA. SSADH activity and protein level were measured. Cell viability, lipid peroxidation, mitochondrial morphology, membrane potential (ΔΨ), and protein markers of mitochondrial stress were evaluated upon Paraquat treatment, in TM and WT transfected cells. TM transfected cells show lower SSADH protein content and activity, fragmented mitochondria, higher levels of peroxidized lipids, and altered ΔΨ than WT transfected cells. Upon Paraquat treatment, TM cells show higher cell death, lipid peroxidation, 4-HNE protein adducts, and lower ΔΨ, than WT transfected cells. These results reinforce the hypothesis that SSADH contributes to cellular antioxidant defense; furthermore, common SNPs may produce unstable, less active SSADH, which could per se negatively affect mitochondrial function and, under oxidative stress conditions, fail to protect mitochondria.

show abstract

Section: Tm Ssadh Affects Mitochondrial Function and Increases Suscepmentioning

confidence: 99%

SSADH Variants Increase Susceptibility of U87 Cells to Mitochondrial Pro-Oxidant Insult

Menduti

Vitaliti

Capo

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…These compounds all contributed to endothelial stress, subendothelial monocyte infiltration, endocytosis of oxLDLs by macrophages, conversion of the latter into foam cells, atheroma formation and maturation of vascular-associated DCs [18]. We identified HNE adducts with heat shock 60 kDa protein 1 (HSP60) in human promyelocytic HL-60 and monocytic THP-1 cell lines exposed to HNE in vitro [131]. Because HSP60 is well known as a vehicle of the presentation of endogenous peptides to T cells [132] and as a target of autoimmune responses in atherosclerosis [133], we proposed that the modification of HSP60 with HNE may both contribute to the oxidative stress-driven inflammation of arterial intima and act as a switchover to immunity-driven chronic inflammation in atherosclerosis [131].…”

Section: Aldehydes and Dna Damage In Inflammationmentioning

confidence: 99%

“…We identified HNE adducts with heat shock 60 kDa protein 1 (HSP60) in human promyelocytic HL-60 and monocytic THP-1 cell lines exposed to HNE in vitro [131]. Because HSP60 is well known as a vehicle of the presentation of endogenous peptides to T cells [132] and as a target of autoimmune responses in atherosclerosis [133], we proposed that the modification of HSP60 with HNE may both contribute to the oxidative stress-driven inflammation of arterial intima and act as a switchover to immunity-driven chronic inflammation in atherosclerosis [131]. The proatherogenic effects of HNE have been further reviewed recently [134],[135].…”

Section: Aldehydes and Dna Damage In Inflammationmentioning

confidence: 99%

DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity

et al. 2017

Self Cite

View full text Add to dashboard Cite

Oxidative stress and lipid peroxidation (LPO) induced by inflammation, excess metal storage and excess caloric intake cause generalized DNA damage, producing genotoxic and mutagenic effects. The consequent deregulation of cell homeostasis is implicated in the pathogenesis of a number of malignancies and degenerative diseases. Reactive aldehydes produced by LPO, such as malondialdehyde, acrolein, crotonaldehyde and 4-hydroxy-2-nonenal, react with DNA bases, generating promutagenic exocyclic DNA adducts, which likely contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. However, reactive aldehydes, when added to tumor cells, can exert an anticancerous effect. They act, analogously to other chemotherapeutic drugs, by forming DNA adducts and, in this way, they drive the tumor cells toward apoptosis. The aldehyde-DNA adducts, which can be observed during inflammation, play an important role by inducing epigenetic changes which, in turn, can modulate the inflammatory process. The pathogenic role of the adducts formed by the products of LPO with biological macromolecules in the breaking of immunological tolerance to self antigens and in the development of autoimmunity has been supported by a wealth of evidence. The instrumental role of the adducts of reactive LPO products with self protein antigens in the sensitization of autoreactive cells to the respective unmodified proteins and in the intermolecular spreading of the autoimmune responses to aldehyde-modified and native DNA is well documented. In contrast, further investigation is required in order to establish whether the formation of adducts of LPO products with DNA might incite substantial immune responsivity and might be instrumental for the spreading of the immunological responses from aldehyde-modified DNA to native DNA and similarly modified, unmodified and/or structurally analogous self protein antigens, thus leading to autoimmunity.

show abstract

“…In fact, unlike free radicals, which have a very short half-life, HNE and other aldehydes deriving from lipid peroxidation can diffuse from the site where they are produced and modulate signalling pathways in other cells. HNE has been reported to induce cell differentiation in human leukemic HL-60 cells and in murine erythroleukemia MEL cells [32], the pathways proposed being different: translocation of PKC, formation of adducts with Heat Shock 60 kDa Protein 1 [51], and inhibition of telomerase activity [52]. In the light of these observations, the supposed involvement of lipid peroxidation products in mediating the anti-cachectic properties of lung cancer cells was investigated.…”

Section: Discussionmentioning

confidence: 99%

4-Hydroxyhexenal and 4-hydroxynonenal are mediators of the anti-cachectic effect of n-3 and n-6 polyunsaturated fatty acids on human lung cancer cells

Muzio

Ricci

Traverso

et al. 2016

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Cachexia, the most severe paraneoplastic syndrome, occurs in about 80% of patients with advanced cancer; it cannot be reverted by conventional, enteral, or parenteral nutrition. For this reason, nutritional interventions must be based on the use of substances possessing, alongside nutritional and energetic properties, the ability to modulate production of the pro-inflammatory factors responsible for the metabolic changes characterising cancer cachexia. In light of their nutritional and anti-inflammatory properties, polyunsaturated fatty acids (PUFAs), and in particular n-3, have been investigated for treating cachexia; however, the results have been contradictory. Since both n-3 and n-6 PUFAs can affect cell functions in several ways, this research investigated the possibility that the effects of both n-3 and n-6 PUFAs could be mediated by their major aldehydic products of lipid peroxidation, 4-hydroxyhexenal (HHE) and 4-hydroxynonenal (HNE), and by their anti-inflammatory properties. An "in vitro" cancer cachexia model, consisting of human lung cancer cells (A427) and murine myoblasts (C2C12), was used. The results showed that: 1) both n-3 and n-6 PUFAs reduced the growth of lung cancer cells without causing cell death, increased lipid peroxidation and Peroxisome Proliferator-Activated Receptor (PPAR)α, and decreased TNFα; 2) culture medium conditioned by A427 cells grown in the absence of PUFAs blocked myosin production and the differentiation of C2C12 muscle cells; conversely, muscle cells grown in culture medium conditioned by the same cells in the presence of PUFAs showed myosin expression and formed myotubes; 3) adding HHE or HNE directly to C2C12 cells maintained in culture medium conditioned by A427 cells in the absence of PUFAs stimulated myosin production and myotube formation; 4) putative consensus sequences for (PPARs) have been found in genes encoding fast isoforms of myosin heavy chain, by a bioinformatics approach. The overall results show, first, the ability of both n-3 and n-6 PUFAs and their lipid peroxidation products to prevent the blocking of myosin expression and myotube formation caused in C2C12 cells by medium conditioned by human lung tumour cells. The C2C12 cell differentiation can be due to direct effect of lipid peroxidation products, as evidenced by treating C2C12 cells with HHE and HNE, and to the decrease of pro-inflammatory TNFα in A427 cell culture medium. The presence of consensus sequences for PPARs in genes encoding the fast isoforms of myosin heavy chain suggests that the effects of PUFAs, HHE, and HNE are PPAR-mediated.

show abstract

Generation of Adducts of 4-Hydroxy-2-nonenal with Heat Shock 60 kDa Protein 1 in Human Promyelocytic HL-60 and Monocytic THP-1 Cell Lines

Cited by 11 publications

References 69 publications

SSADH Variants Increase Susceptibility of U87 Cells to Mitochondrial Pro-Oxidant Insult

SSADH Variants Increase Susceptibility of U87 Cells to Mitochondrial Pro-Oxidant Insult

DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity

4-Hydroxyhexenal and 4-hydroxynonenal are mediators of the anti-cachectic effect of n-3 and n-6 polyunsaturated fatty acids on human lung cancer cells

Contact Info

Product

Resources

About