The deubiquitinase USP7 regulates oxidative stress through stabilization of HO-1

Gao, Ming; Qi, Zijuan; Deng, Min; Huang, Hongyang; Xu, Zhijie; Guo, Guijie; Jing, Jiajun; Huang, Xiaofeng; Xu, Ming; Kloeber, Jake A.; Liu, Sijin; Huang, Jinzhou; Lou, Zhenkun; Han, Jinxiang

doi:10.1038/s41388-022-02403-w

Cited by 14 publications

(4 citation statements)

References 42 publications

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“…Previous studies have shown that the E3 ubiquitin ligase TRC8 and the deubiquitinase USP7 can regulate the protein level of HMOX1 through ubiquitination or deubiquitination [46,47]. Although HMOX1 is considered as a protective antioxidant enzyme that protects the cells from damage by inhibiting oxidative stress [48,49].…”

Section: Discussionmentioning

confidence: 99%

RNF181 promotes ferroptosis by ubiquitinating HMOX1 to inhibit gastric cancer cell proliferation and chemoresistance

Cui,

Zhou,

Chen

et al. 2024

Preprint

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Emergence of chemotherapeutic resistance remains an important challenge in cancer treatment, especially in advanced cancers. Recent studies have shown that ferroptosis is closely associated with tumor chemoresistance, and induction of ferroptosis has been shown to reverse chemoresistance. This study focused on the important function of Ring Finger Protein 181 (RNF181) in gastric cancer and the potential mechanisms involved in chemoresistance. Here, we found that RNF181 was aberrantly activated in chemoresistant cells of gastric cancer, and high expression of RNF181 was associated with poor patient prognosis. Depletion of RNF181 inhibited the proliferation and tumorigenicity of chemoresistant cells, and increased chemotherapeutic drug sensitivity. Mechanistically, our study showed that the interaction between RNF181 and HMOX1 mediated K27-linked polyubiquitination of HMOX1 and regulated its protein stability. Upregulation of HMOX1 expression after knockdown of RNF181 resulted in excessive heme degradation and intracellular iron overload to promote ferroptosis. Generally, our study reveals the important role of RNF181 in chemoresistance in gastric cancer, and targeting RNF181 may be a rational strategy to improve the efficacy of chemotherapy in gastric cancer.

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Section: Discussionmentioning

confidence: 99%

RNF181 promotes ferroptosis by ubiquitinating HMOX1 to inhibit gastric cancer cell proliferation and chemoresistance

Cui,

Zhou,

Chen

et al. 2024

Preprint

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“…Enzymes involved in antioxidant/phase II detoxification contribute to protection by regulating the intracellular redox state ( Li et al, 2008 ). The initial stepwise breakdown of heme is catalyzed by HO-1, producing powerful antioxidants such as free iron, carbon monoxide, and biliverdin ( Gao et al, 2022 ). NQO1 detoxifies reactive quinones to its less harmful hydroquinones, protecting cells from oxidative stress ( Ross and Siegel, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Protective effect of dexmedetomidine against delayed bone healing caused by morphine via PI3K/Akt mediated Nrf2 antioxidant defense system

Lou,

Zou,

Shen

et al. 2024

Front. Pharmacol.

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BackgroundAs a class of analgesics, opioids are frequently used to treat both acute and chronic moderate to severe pain. Patients frequently receive opioid painkillers after orthopedic accidents or surgeries. Evidence suggests that opioid drug users have a 55.1% higher risk of fracture and poor bone repair than non-users of opioid drugs. The key pathogenic alterations in the incidence and progression of poor bone repair are over apoptosis and aging of osteoblasts due to the stress caused by oxidation. Dexmedetomidine (Dex) has been proven to protect against a variety of degenerative illnesses by reducing oxidative stress. However, nothing is known about how it affects bone repair.MethodsPI3K/Akt/Nrf2 pathway was detected by immunofluorescence and Western blot. SOD, CAT, JC-1, dihydroethidium and mitosox were used in the Oxidative Stress. Micro-CT, H&E and Masson’s staining, immunohistochemically were performed to evaluate the therapeutic effects of DEX on calvarial defects in the morphine-induced rat model.ResultsWe found that morphine-induced an imbalance in the metabolism and catabolism of primary rat Osteoblasts. However, these conditions could be inhibited by DEX treatment. In the meantime, DEX induced the expression of Nrf2-regulated antioxidant enzymes such as NQO1, HO-1, GCLm, GCLc, and TrxR1. DEX-mediated Nrf2 activation is linked to the PI3K/Akt signaling system. Furthermore, it has been established that intravenous DEX enhanced the growth of bone healing in a model of a surgically produced rat cranial lesion.ConclusionThis is the first description of the unique DEX mechanism acting as a Nrf2 activator against morphine-mediated oxidative harm, raising the possibility that the substance may be used to prevent bone defects.

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“…After CDCA treatment, the activity of various transcription factors in GES-1 cells was changed, and the result showed that NFE2 was increased [14]. HO-1 as a downstream gene of NRF2 has a cytoprotective efect in normal tissues via restraining oxidative dysregulation, inappropriate immune response, and related disorders, especially in cancer carcinogenesis [52,54]. Much data report and in vivo studies revealed the increased expression of the HO-1 enzyme in tumors compared with the surrounding normal tissues [55].…”

Section: Discussionmentioning

confidence: 99%

Dendrobium officinale Polysaccharides Inhibit CDCA-Induced Gastric Intestinal Metaplasia through Activating NRF2/HO-1 and Modulating HNF4α/CDX2 Signaling Pathway

Zhao,

Huang,

Wang

et al. 2023

Journal of Food Biochemistry

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Bile reflux (BR) was considered to be an independent risk factor for the development of precancerous gastric lesions and GC. Dendrobium officinale polysaccharides (DOP) show a novel potential in preventing the progress of gastric cancer. However, the specific mechanism of DOP that causes such activities remains a mystery. This study aimed to investigate the effects of DOP on chenodeoxycholic acid (CDCA)-induced gastric intestinal metaplasia and explore the underlying mechanisms. Different concentrations of DOP had no significant damage to normal GSE-1 cells and gastric intestinal metaplasia model cells by CCK-8 assay. After DOP treatment, the mRNA and protein expression of CDX2 ( p < 0.01) and HNF4α ( p < 0.01) were decreased, and HO-1 ( p < 0.05) and TFF2 ( p < 0.01) were increased. The NRF2 protein expression was slightly upregulated ( p < 0.05), and H-DOP further promoted NRF2 protein expression in the nucleus ( p < 0.05). Hence, our findings reveal that DOP could be used as a potential anti-inflammation supplement by activating NRF2/HO-1 and modulating the HNF4α/CDX2 signaling pathway to inhibit the progress of CDCA-induced gastric intestinal metaplasia.

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The deubiquitinase USP7 regulates oxidative stress through stabilization of HO-1

Cited by 14 publications

References 42 publications

RNF181 promotes ferroptosis by ubiquitinating HMOX1 to inhibit gastric cancer cell proliferation and chemoresistance

RNF181 promotes ferroptosis by ubiquitinating HMOX1 to inhibit gastric cancer cell proliferation and chemoresistance

Protective effect of dexmedetomidine against delayed bone healing caused by morphine via PI3K/Akt mediated Nrf2 antioxidant defense system

Dendrobium officinale Polysaccharides Inhibit CDCA-Induced Gastric Intestinal Metaplasia through Activating NRF2/HO-1 and Modulating HNF4α/CDX2 Signaling Pathway

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