Reply to Richarme: Evidence against a role of DJ-1 in methylglyoxal detoxification

Pfaff, Daniel; Fleming, Thomas; Nawroth, Peter P.; Teleman, Aurelio A.

doi:10.1074/jbc.l117.798579

Cited by 7 publications

(4 citation statements)

References 4 publications

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“…It is a type of protein containing 189 amino acids, which was initially identified as an oncogene binding to Harvey-rat sarcoma (H-Ras) and can transform mouse NIH3T3 cells [9]. DJ-1 protein has been found in a variety of malignant tumor cells, including prostate cancer, non-small-cell lung cancer, laryngeal cancer, ovarian cancer, and cervical cancer, and it plays a vital role in promoting cell proliferation and metastasis [10][11][12][13]. Several studies have indicated that DJ-1 protein expression is reduced after the human lung cancer NCI-H157 cell line is treated with paclitaxel and MEK inhibitor U0126.…”

Section: Introductionmentioning

confidence: 99%

A Study on Curcumol Influencing Proliferation and Apoptosis of Hepatocellular Carcinoma Cells through DJ-1/PTEN/PI3K/AKT Pathway

Zhang

Zhong

Sun

et al. 2022

BioMed Research International

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Objective. To study the mechanism of curcumol affecting the proliferation and apoptosis of liver cancer cells through the DJ-1/PTEN/PI3K/AKT pathway. Method. HepG2 cells were cultured in vitro, treated with curcumol at concentrations of 10, 30, and 100 μg/mL, and DMSO was used as a control. The levels of cell proliferation and apoptosis were measured by CCK-8 and flow cytometry, respectively. RT-PCR and western blot were used to detect PTEN, p-AKT, DJ-1, and PI3K gene and protein expression changes. Result. (1) Compared with the DMSO blank control group, the proliferation level of liver cancer cells in the 10 μg/mL curcumol group decreased, and the proportion of apoptosis increased (p <0.05). (2) Compared with the blank control group and the 10 and 30 μg/mL concentration groups, the proliferation level of liver cancer cells in the 100 μg/mL curcumol group was significantly reduced, and the proportion of cell apoptosis was significantly increased ( p < 0.05 ). (3) Curcumol can significantly increase the expression of PTEN gene and protein in liver cancer cells and reduce the expression of DJ-1 and PI3K genes and protein in liver cancer cells ( p < 0.05 ). Conclusion. Curcumol can regulate DJ-1, PTEN, PI3K, and AKT signal transduction pathways, inhibit cell proliferation, and cause a significant increase in the proportion of cell apoptosis, and the pharmacodynamic effect of curcumol is dependent on the time and dose of action.

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Section: Introductionmentioning

confidence: 99%

A Study on Curcumol Influencing Proliferation and Apoptosis of Hepatocellular Carcinoma Cells through DJ-1/PTEN/PI3K/AKT Pathway

Zhang

Zhong

Sun

et al. 2022

BioMed Research International

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“…These studies seemed to represent a potential breakthrough, since they suggested that Parkinson’s disease might be caused by the failure to maintain proteins and DNA “clean” and functional. More recently, these findings have been disputed ( 41 , 42 ), and convincing evidence has been presented that this apparent deglycating activity is not due to the active removal of these adducts, but rather due to the degradation of free methylglyoxal, which is in rapid equilibrium with these modifications ( 43 , 44 ). Consistent with this, we did not observe an increase of methylglyoxal-modified proteins or nucleotides in several PARK7 knockout cell lines ( SI Appendix , Fig.…”

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confidence: 99%

Parkinson's disease protein PARK7 prevents metabolite and protein damage caused by a glycolytic metabolite

Heremans

Caligiore

Gerin

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Cells are continuously exposed to potentially dangerous compounds. Progressive accumulation of damage is suspected to contribute to neurodegenerative diseases and aging, but the molecular identity of the damage remains largely unknown. Here we report that PARK7, an enzyme mutated in hereditary Parkinson’s disease, prevents damage of proteins and metabolites caused by a metabolite of glycolysis. We found that the glycolytic metabolite 1,3-bisphosphoglycerate (1,3-BPG) spontaneously forms a novel reactive intermediate that avidly reacts with amino groups. PARK7 acts by destroying this intermediate, thereby preventing the formation of proteins and metabolites with glycerate and phosphoglycerate modifications on amino groups. As a consequence, inactivation of PARK7 (or its orthologs) in human cell lines, mouse brain, and Drosophila melanogaster leads to the accumulation of these damaged compounds, most of which have not been described before. Our work demonstrates that PARK7 function represents a highly conserved strategy to prevent damage in cells that metabolize carbohydrates. This represents a fundamental link between metabolism and a type of cellular damage that might contribute to the development of Parkinson’s disease.

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“…Further work by one of these groups suggested that DJ-1 could also deglycate guanine nucleotides in DNA and RNA . These findings have been contradicted by follow-up studies suggesting that the reported deglycase activity of DJ-1 may result from a buffer artifact or spontaneous breakdown of glycated molecules (Andreeva et al, 2019;Pfaff et al, 2017a;Pfaff et al, 2017b). While it is generally agreed that DJ-1 plays a role in protecting cells from glycation damage, further work is required to identify whether its primary role is to detoxify the unconjugated reactive molecules as a glyoxylase or to undo their damage to endogenous biomolecules as a deglycase (Jun and Kool, 2020).…”

Section: Cytosolic Substrates Of Parkin and Pink1mentioning

confidence: 99%

The cell biology of Parkinson’s disease

Panicker

Dawson

et al. 2021

Journal of Cell Biology

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Parkinson’s disease (PD) is a progressive neurodegenerative disorder resulting from the death of dopamine neurons in the substantia nigra pars compacta. Our understanding of PD biology has been enriched by the identification of genes involved in its rare, inheritable forms, termed PARK genes. These genes encode proteins including α-syn, LRRK2, VPS35, parkin, PINK1, and DJ1, which can cause monogenetic PD when mutated. Investigating the cellular functions of these proteins has been instrumental in identifying signaling pathways that mediate pathology in PD and neuroprotective mechanisms active during homeostatic and pathological conditions. It is now evident that many PD-associated proteins perform multiple functions in PD-associated signaling pathways in neurons. Furthermore, several PARK proteins contribute to non–cell-autonomous mechanisms of neuron death, such as neuroinflammation. A comprehensive understanding of cell-autonomous and non–cell-autonomous pathways involved in PD is essential for developing therapeutics that may slow or halt its progression.

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Reply to Richarme: Evidence against a role of DJ-1 in methylglyoxal detoxification

Cited by 7 publications

References 4 publications

A Study on Curcumol Influencing Proliferation and Apoptosis of Hepatocellular Carcinoma Cells through DJ-1/PTEN/PI3K/AKT Pathway

A Study on Curcumol Influencing Proliferation and Apoptosis of Hepatocellular Carcinoma Cells through DJ-1/PTEN/PI3K/AKT Pathway

Parkinson's disease protein PARK7 prevents metabolite and protein damage caused by a glycolytic metabolite

The cell biology of Parkinson’s disease

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