NAD(P)H quinone oxidoreductase 1 inhibits the proteasomal degradation of homocysteine-induced endoplasmic reticulum protein

Maeda, Tomoji; Tanabe-Fujimura, Chiaki; Fujita, Yu; Abê, Chiaki; Nanakida, Yoshino; Zou, Kun; Liu, Junjun; Nakajima, Takeshi; Komano, Hiroto

doi:10.1016/j.bbrc.2016.04.057

Cited by 10 publications

(5 citation statements)

References 25 publications

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“…To elucidate the reason for p53, the NQO1 enzyme, protein, and mRNA expression were investigated. NQO1 is responsible for detoxification of several natural and synthetic compounds by two-electron reduction and the stability of tumor suppressor proteins p53 (53)(54)(55). Molecular studies proved that NQO1 enzyme activity significantly elevated in many solid tumors, which suggests its crucial importance in cancer therapy (56).…”

Section: Resultsmentioning

confidence: 99%

Upregulation of p53 by tannic acid treatment suppresses the proliferation of human colorectal carcinoma

2021

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The present study’s objective is to clarify the molecular mechanisms of tannic acid effects on the viability of human colorectal carcinoma (CRC). Tannic acid is stable for up to 48 h and is localized in both cytoplasm and nucleus. It dose-dependently inhibited the viability of CRC cell lines; SW-620 and HT-29 with IC 50 values of 7.2 ± 0.8 and 37.6 ± 1.4 µmol L–1. Besides, metastatic, invasive, and colony formation properties of CRC cells were significantly inhibited following the tannic acid treatment (p < 0.001). Tannic acid has been found to modulate enzyme, protein, and gene expressions of NQO1 in different levels and the upregulation of protein/gene expressions of p53 (p < 0.001), which leads the cells to trigger apoptosis. In conclusion, the present in vitro study may supply a significant background for in vivo studies in which the molecular mechanisms of antioxidant and chemopreventive activities of tannic acid will completely clarify.

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Section: Resultsmentioning

confidence: 99%

Upregulation of p53 by tannic acid treatment suppresses the proliferation of human colorectal carcinoma

2021

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“…ER stress induces NEDD4 expression via E3 ubiquitin ligase [49,68], tightly in combination with HRD1 or SYVN1 [69]. Furthermore, NADPH oxidase, OSrelated enzyme, Mdm2-p53 pathway, and glutamate receptor subunit 1 (GluA1) are related to ER stress-induced NEDD4 expression [70][71][72][73][74][75] and HMG-CoA reductase down-regulation [68]. NEDD4 indirectly down-regulates phosphatidyl inositol 3-kinase (PI3K) [76] but especially targets phosphatase and tensin homologue (PTEN) [45] and is activated via LDL receptors [77].…”

Section: Molecular Pathogenesis Of Hyperlipidemiamentioning

confidence: 99%

Therapeutic Properties of Polyphenols Affect AMPK Molecular Pathway in Hyperlipidemia

Sotoudeheian¹,

Hoseini²,

Mirahmadi³

2023

Preprint

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Hyperlipidemia is the fat particles excess in the serum. Hyperlipidemia increases the mortality rate that occurs with other metabolic disorders. Hyperlipidemia is classified into familial and acquired subgroups. Moreover, Hyperlipidemia etiology is based on environmental or genetic factors. For instance, abnormal HMG-CoA regulation down-regulates ubiquitin ligase and targets variable oxidative stress-related condition proteins. There has been proven reactive oxygen species (ROS) overshoot happens during hyperlipidemia occurrence. OS, directly and indirectly, regulates molecular cascades within the cell and leads to gene expression alteration. At this molecular juncture, AMPK is affected by ROS. AMPK is a serine-threonine kinase and a critical energy balance. Low energy conditions result in AMPK activation due to the down-regulation of protein and lipid synthesis. Furthermore, ER stress and activated unfolded protein proteasomal response and autophagy are AMPK mediated. Polyphenols are widespread dietary plant-based compounds that regulate gene expression and signal conduction. Through the hyperlipidemic state, FFAs releasing indirectly connect to AMPK/NF-κB pathway then polyphenols target them. AMPK, during this FFA exposure, down-regulates de novo lipid molecules generation. Likewise, if AMPK/mTOR pathway failure is prolonged, the hyperlipidemic state may be explicit, activated by natural herbal mediators, e.g., polyphenols. Polyphenols activate the AMPK signaling pathway and influence lipid metabolism. Polyphenol-mediated AMPK activation results in lipogenesis inhibition and lipophagy. Cholesterol efflux mediated polyphenols lipid-lowering effects, accessing LXR pathway. All these clues persist on direct or indirect AMPK-related polyphenolic anti-hyperlipidemic effects.

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“…Herp’s cellular half-life is increased by NQO1. [ 186 , 187 ] PGC-1α Stabilizes this intrinsically disordered protein and protects it from proteasomal degradation. Enhances interaction Antagonizes interaction Cellular levels of NQO1 and PGC-1α are correlated.…”

Section: Table A1mentioning

confidence: 99%

Targeting HIF-1α Function in Cancer through the Chaperone Action of NQO1: Implications of Genetic Diversity of NQO1

Salido

Timson

Betancor-Fernández

et al. 2022

JPM

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HIF-1α is a master regulator of oxygen homeostasis involved in different stages of cancer development. Thus, HIF-1α inhibition represents an interesting target for anti-cancer therapy. It was recently shown that the HIF-1α interaction with NQO1 inhibits proteasomal degradation of the former, thus suggesting that targeting the stability and/or function of NQO1 could lead to the destabilization of HIF-1α as a therapeutic approach. Since the molecular interactions of NQO1 with HIF-1α are beginning to be unraveled, in this review we discuss: (1) Structure–function relationships of HIF-1α; (2) our current knowledge on the intracellular functions and stability of NQO1; (3) the pharmacological modulation of NQO1 by small ligands regarding function and stability; (4) the potential effects of genetic variability of NQO1 in HIF-1α levels and function; (5) the molecular determinants of NQO1 as a chaperone of many different proteins including cancer-associated factors such as HIF-1α, p53 and p73α. This knowledge is then further discussed in the context of potentially targeting the intracellular stability of HIF-1α by acting on its chaperone, NQO1. This could result in novel anti-cancer therapies, always considering that the substantial genetic variability in NQO1 would likely result in different phenotypic responses among individuals.

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NAD(P)H quinone oxidoreductase 1 inhibits the proteasomal degradation of homocysteine-induced endoplasmic reticulum protein

Cited by 10 publications

References 25 publications

Upregulation of p53 by tannic acid treatment suppresses the proliferation of human colorectal carcinoma

Upregulation of p53 by tannic acid treatment suppresses the proliferation of human colorectal carcinoma

Therapeutic Properties of Polyphenols Affect AMPK Molecular Pathway in Hyperlipidemia

Targeting HIF-1α Function in Cancer through the Chaperone Action of NQO1: Implications of Genetic Diversity of NQO1

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