BNIP3 as a Regulator of Cisplatin-Induced Apoptosis

Горбунова, А. С.; Denisenko, Tatiana V.; Yapryntseva, Maria A.; Pivnyuk, Anastasia D; Prikazchikova, Tatiana; Gogvadze, Vladimir; Zhivotovsky, Boris

doi:10.1134/s0006297920100120

Cited by 8 publications

(13 citation statements)

References 31 publications

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“…The role of BNIP3 in cell death is controversial. BNIP3 induces apoptosis and mitophagy, or even stimulates cell proliferation (Lin et al 2021 ; Gorbunova et al 2020 ). Fundamentally, cell type and environment determine the interdependence between autophagy and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

BNIP3 mediates the different adaptive responses of fibroblast-like synovial cells to hypoxia in patients with osteoarthritis and rheumatoid arthritis

Deng

Wang

et al. 2022

Mol Med

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Background Hypoxia is one of the important characteristics of synovial microenvironment in rheumatoid arthritis (RA), and plays an important role in synovial hyperplasia. In terms of cell survival, fibroblast-like synovial cells (FLSs) are relatively affected by hypoxia. In contrast, fibroblast-like synovial cells from patients with RA (RA-FLSs) are particularly resistant to hypoxia-induced cell death. The purpose of this study was to evaluate whether fibroblast-like synovial cells in patients with osteoarthritis (OA-FLSs) and RA-FLSs have the same adaptation to hypoxia. Methods CCK-8, flow cytometry and BrdU were used to detect the proliferation of OA-FLSs and RA-FLSs under different oxygen concentrations. Apoptosis was detected by AV/PI, TUNEL and Western blot, mitophagy was observed by electron microscope, laser confocal microscope and Western blot, the state of mitochondria was detected by ROS and mitochondrial membrane potential by flow cytometry, BNIP3 and HIF-1α were detected by Western blot and RT-qPCR. The silencing of BNIP3 was achieved by stealth RNA system technology. Results After hypoxia, the survival rate of OA-FLSs decreased, while the proliferation activity of RA-FLSs further increased. Hypoxia induced an increase in apoptosis and inhibition of mitophagy in OA-FLSs, but not in RA-FLSs. Hypoxia led to a more lasting adaptive response. RA-FLSs displayed a more significant increase in the expression of genes transcriptionally regulated by HIF-1α. Interestingly, they showed higher BNIP3 expression than OA-FLSs, and showed stronger mitophagy and proliferation activities. BNIP3 siRNA experiment confirmed the potential role of BNIP3 in the survival of RA-FLSs. Inhibition of BNIP3 resulted in the decrease of cell proliferation, mitophagy and the increase of apoptosis. Conclusion In summary, RA-FLSs maintained intracellular redox balance through mitophagy to promote cell survival under hypoxia. The mitophagy of OA-FLSs was too little to maintain the redox balance of mitochondria, resulting in apoptosis. The difference of mitophagy between OA-FLSs and RA-FLSs under hypoxia is mediated by the level of BNIP3 expression.

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Section: Introductionmentioning

confidence: 99%

BNIP3 mediates the different adaptive responses of fibroblast-like synovial cells to hypoxia in patients with osteoarthritis and rheumatoid arthritis

Deng

Wang

et al. 2022

Mol Med

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“…Interestingly, as an important demethylase, FTO promotes apoptosis and participates in the occurrence of cancer by regulating downstream targets BNIP3, MZF1, MYC, and PGC-1 α ( Liu et al, 2018 ; Su et al, 2018 ; Niu et al, 2019 ; Zhuang et al, 2019 ). BNIP3 is considered to be a pro-apoptotic member of the Bcl-2 apoptotic protein family ( Gorbunova et al, 2020 ). In breast cancer, the expression of FTO is up-regulated while that of BNIP3 is down-regulated ( Niu et al, 2019 ).…”

Section: The Role Of M 6 a In Pcdmentioning

confidence: 99%

m6A: An Emerging Role in Programmed Cell Death

Tang

Chen

et al. 2022

Front. Cell Dev. Biol.

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Programmed cell death is an active extinction process, including autophagy, ferroptosis, pyroptosis, apoptosis, and necroptosis. m6A is a reversible RNA modification which undergoes methylation under the action of methylases (writers), and is demethylated under the action of demethylases (erasers). The RNA base site at which m6A is modified is recognized by specialized enzymes (readers) which regulate downstream RNA translation, decay, and stability. m6A affects many aspects of mRNA metabolism, and also plays an important role in promoting the maturation of miRNA, the translation and degradation of circRNA, and the stability of lncRNA. The regulatory factors including writers, erasers and readers promote or inhibit programmed cell death via up-regulating or down-regulating downstream targets in a m6A-dependent manner to participate in the process of disease. In this review, we summarize the functions of m6A with particular reference to its role in programmed cell death.

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“…Platinum-based metallodrugs are powerful agents in the treatment of cancer. The use of these chemotherapeutics has been correlated with the release of Cyt c in the cytosol and subsequent apoptosis [ 74 – 76 ]. Other drugs that involve Cyt c as part of their mechanism are organic compounds, such as lonidamine, pristimerin, teniposide and 5-fluorouoracil.…”

Section: Biomedical Applications Of Cyt C In Cancer Researchmentioning

confidence: 99%

“…Cisplatin is the parent Pt(II) anticancer drug used in chemotherapy for the treatment of various types of cancer, including advanced bladder cancer and metastatic ovarian and testicular cancer. It binds to the G bases of DNA and forms crosslinks with GG sequences [ 77 ], causing DNA damage, interfering with DNA repair mechanisms, and inducing mitochondria-mediated apoptosis in cancer cells [ 74 , 76 ]. The initial cancer patient response to cisplatin is high.…”

Section: Biomedical Applications Of Cyt C In Cancer Researchmentioning

confidence: 99%

Cytochrome c: Using Biological Insight toward Engineering an Optimized Anticancer Biodrug

et al. 2021

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The heme protein cytochrome c (Cyt c) plays pivotal roles in cellular life and death processes. In the respiratory chain of mitochondria, it serves as an electron transfer protein, contributing to the proliferation of healthy cells. In the cell cytoplasm, it activates intrinsic apoptosis to terminate damaged cells. Insight into these mechanisms and the associated physicochemical properties and biomolecular interactions of Cyt c informs on the anticancer therapeutic potential of the protein, especially in its ability to subvert the current limitations of small molecule-based chemotherapy. In this review, we explore the development of Cyt c as an anticancer drug by identifying cancer types that would be receptive to the cytotoxicity of the protein and factors that can be finetuned to enhance its apoptotic potency. To this end, some information is obtained by characterizing known drugs that operate, in part, by triggering Cyt c induced apoptosis. The application of different smart drug delivery systems is surveyed to highlight important features for maintaining Cyt c stability and activity and improving its specificity for cancer cells and high drug payload release while recognizing the continuing limitations. This work serves to elucidate on the optimization of the strategies to translate Cyt c to the clinical market.

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BNIP3 as a Regulator of Cisplatin-Induced Apoptosis

Cited by 8 publications

References 31 publications

BNIP3 mediates the different adaptive responses of fibroblast-like synovial cells to hypoxia in patients with osteoarthritis and rheumatoid arthritis

BNIP3 mediates the different adaptive responses of fibroblast-like synovial cells to hypoxia in patients with osteoarthritis and rheumatoid arthritis

m6A: An Emerging Role in Programmed Cell Death

Cytochrome c: Using Biological Insight toward Engineering an Optimized Anticancer Biodrug

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