Involvement of mitophagy in cisplatin-induced cell death regulation

Abdrakhmanov, Alibek; Куликов, А. В.; Luchkina, Ekaterina A.; Zhivotovsky, Boris; Gogvadze, Vladimir

doi:10.1515/hsz-2018-0210

Cited by 26 publications

(20 citation statements)

References 35 publications

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“…We investigated whether hUMSC transplantation affects stromal cell differentiation through the TGF-β 1 signaling pathway. In order to find the appropriate concentration of CDDP and TGF-β 1 inhibitor SB431542 to treat stromal cells, according to previous reports, the CCK-8 kit was used to detect the viability of stromal cells at different concentrations [ 34 – 36 ]. The CDDP concentration at 20 μM was selected since the treatment resulted in the cell viability as 82.82% (Fig.…”

Section: Resultsmentioning

confidence: 99%

hUMSCs regulate the differentiation of ovarian stromal cells via TGF-β1/Smad3 signaling pathway to inhibit ovarian fibrosis to repair ovarian function in POI rats

et al. 2020

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Objective The basic pathological changes of primary ovarian insufficiency (POI) include ovarian tissue fibrosis and follicular development disorders. The human umbilical cord mesenchymal stem cell (hUMSC) transplantation has been shown an effective method to improve the ovarian function in POI rat model; however, the exact mechanisms are still unclear. The purpose of this study is to investigate whether the recovery of ovarian function in POI rats is related to the inhibition of tissue fibrosis following hUMSC transplantation. Furthermore, the transforming growth factor-β1 (TGF-β1) signaling pathway is explored to determine the mechanisms of ovarian function recovery through its inhibition of tissue fibrosis. Methods The primary ovarian insufficiency (POI) rat model was established by intraperitoneal injection of chemotherapy drug cisplatin (CDDP) for 7 days. The levels of serum sex hormones were measured using enzyme-linked immunosorbent assay (ELISA). The tissue fibrosis in the ovary was examined using Masson staining and Sirius red staining. The collagen fibers in the ovarian tissues were detected by Western blot analysis. To investigate the mechanisms of ovarian function recovery following hUMSC transplantation, ovarian stromal cells were isolated from the ovarian cortex of immature rats. The expression of Cytochrome P450 17A1 (Cyp17a1) and fibrosis marker of alpha smooth muscle actin (α-SMA) in ovarian stromal cells was examined using immunofluorescence analysis. Also, the protein levels of Cyp17a1 and α-SMA in ovarian stromal cells were examined by Western blot analysis. The expression of TGF-β1 and Smad3 signals was measured by Western blot and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis. Results The results show that the function of the ovary in POI rats was significantly improved after hUMSC transplantation. The expression of fibrosis markers (α-SMA) and production of Collagen Type I (Collagen I) and Collagen Type III (Collagen III) in POI rats were significantly inhibited in POI rats following hUMSC transplantation. In the cultured ovarian stromal cells, the decrease of TGF-β1 and p-Smad3 protein expression was observed in hUMSC-treated POI rats. The treatment with TGF-β1 inhibitor of SB431542 further confirmed this signal pathway was involved in the process. Conclusion Our study demonstrated that the TGF-β1/Smad3 signaling pathway was involved in the inhibition of ovarian tissue fibrosis, which contributed to the restoration of ovarian function in POI rats following hUMSC transplantation.

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Section: Resultsmentioning

confidence: 99%

hUMSCs regulate the differentiation of ovarian stromal cells via TGF-β1/Smad3 signaling pathway to inhibit ovarian fibrosis to repair ovarian function in POI rats

et al. 2020

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“…This assumption is supported by several examples where the genetic inhibition of mitophagy pathways sensitize cancer cells towards cell death induced by anticancer treatments [293,294]. In fact, autophagy (and mitophagy by extension) is highly sensitive to microtubule-dynamics modulators since microtubules are essential for the autophagosome fusion with the lysosome [295,296].…”

Section: Mitophagy and Anti-cancer Therapiesmentioning

confidence: 99%

Mitophagy in Cancer: A Tale of Adaptation

Vara-Pérez

Felipe‐Abrio

Agostinis

2019

Cells

180

134

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In the past years, we have learnt that tumors co-evolve with their microenvironment, and that the active interaction between cancer cells and stromal cells plays a pivotal role in cancer initiation, progression and treatment response. Among the players involved, the pathways regulating mitochondrial functions have been shown to be crucial for both cancer and stromal cells. This is perhaps not surprising, considering that mitochondria in both cancerous and non-cancerous cells are decisive for vital metabolic and bioenergetic functions and to elicit cell death. The central part played by mitochondria also implies the existence of stringent mitochondrial quality control mechanisms, where a specialized autophagy pathway (mitophagy) ensures the selective removal of damaged or dysfunctional mitochondria. Although the molecular underpinnings of mitophagy regulation in mammalian cells remain incomplete, it is becoming clear that mitophagy pathways are intricately linked to the metabolic rewiring of cancer cells to support the high bioenergetic demand of the tumor. In this review, after a brief introduction of the main mitophagy regulators operating in mammalian cells, we discuss emerging cell autonomous roles of mitochondria quality control in cancer onset and progression. We also discuss the relevance of mitophagy in the cellular crosstalk with the tumor microenvironment and in anti-cancer therapy responses.

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“…We chose CCK-8 and mRFP-GFP-LC3 assays to determine the autophagy levels. Concentrations of CDDP assessed using CCK-8 and exposures time were selected based on previous reports [34][35][36]. TICs were incubated with varying concentrations of CDDP (0, 5, 10, 15, 20, 40, or 60 μM) for 24 h (Fig.…”

Section: Effects Of Cddp Treatment On Autophagy In Ticsmentioning

confidence: 99%

hUMSC transplantation restores ovarian function in POI rats by inhibiting autophagy of theca-interstitial cells via the AMPK/mTOR signaling pathway

Bao

Cui

et al. 2020

Stem Cell Res Ther

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Background: Previous studies of primary ovarian insufficiency (POI) have focused on granulosa cells (GCs) and ignored the role of theca-interstitial cells (TICs). This study aims to explore the mechanism of the protective effects of human umbilical cord-derived mesenchymal stem cells (hUMSCs) on ovarian function in POI rats by regulating autophagy of TICs. Methods: The POI model was established in rats treated with cisplatin (CDDP). The hUMSCs were transplanted into POI rats by tail vein. Enzyme-linked immunosorbent assay (ELISA) analysis, hematoxylin and eosin (HE) staining, and immunohistochemistry were used to measure the protective effects of hUMSCs. The molecular mechanisms of injury and repairment of TICs were assessed by immunofluorescence, transmission electron microscope (TEM), flow cytometry (FCM), western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). Results: In vivo, hUMSC transplantation restored the ovarian function and alleviated the apoptosis of TICs in POI rats. In vitro, hUMSCs reduced the autophagy levels of TICs by reducing oxidative stress and regulating AMPK/mTOR signaling pathway, thereby alleviating the apoptosis of TICs. Conclusion: This study indicates that hUMSCs protected ovarian function in POI by regulating autophagy signaling pathway AMPK/mTOR.

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Involvement of mitophagy in cisplatin-induced cell death regulation

Cited by 26 publications

References 35 publications

hUMSCs regulate the differentiation of ovarian stromal cells via TGF-β1/Smad3 signaling pathway to inhibit ovarian fibrosis to repair ovarian function in POI rats

hUMSCs regulate the differentiation of ovarian stromal cells via TGF-β1/Smad3 signaling pathway to inhibit ovarian fibrosis to repair ovarian function in POI rats

Mitophagy in Cancer: A Tale of Adaptation

hUMSC transplantation restores ovarian function in POI rats by inhibiting autophagy of theca-interstitial cells via the AMPK/mTOR signaling pathway

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