Melatonin protects mouse testes from palmitic acid‐induced lipotoxicity by attenuating oxidative stress and DNA damage in a SIRT1‐dependent manner

Xu, Dejun; Liu, Lingbin; Zhao, Yongju; Yang, Li; Cheng, Jianyong; Hua, Rongmao; Zhang, Zelin; Li, Qingwang

doi:10.1111/jpi.12690

Cited by 139 publications

(93 citation statements)

References 66 publications

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“…Similarly, previous study con rmed that isorhamnetin inhibited collagen deposition in N2a cells by alleviating ERS [26]. ERS could disturb the balance of Ca2+ [27]. Research have shown that isorhamnetin inhibited Ca2+ overload and alleviated ERS-induced apoptosis in N2a cells [26].…”

Section: Discussionsupporting

confidence: 53%

Isorhamnetin Protects Zearalenone-induced Damage via the PI3K/Akt Signaling Pathway in Porcine Granulosa Cells

Chen

Zhang

et al. 2021

Preprint

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Background: Zearalenone (ZEA) is widely derived from moldy cereal grain, which has adverse effects on animal reproduction. In particular, pigs are more sensitive to ZEA-induced toxicity than other animals. Isorhamnetin, a flavonoid has extensive of pharmacological activities. However, little is known about the effects of isorhamnetin on reproduction. Thus, it would be interesting to clarify the effect and the underlying molecular mechanism of isorhamnetin involvement in ZEA-induced cytotoxicity in porcine granulosa cells.Results: Our findings showed that isorhamnetin suppressed ZEA-induced apoptosis by regulating Bcl-2 and Bax protein changes. Changes in intracellular Ca2+ levels and CHOP, ATF6, GRP78 indicated that isorhamnetin rescued ZEA-induced endoplasmic reticulum stress (ERS). Furthermore, isorhamnetin prevented ZEA-induced reactive oxygen species (ROS) via P38 signaling pathway. Mechanistically, isorhamnetin stimulated the expression of PCNA and CyclinD, thereby raising the ratio of S phases cells in response to ZEA-induced apoptosis via PI3K/Akt signaling pathway. Isorhamnetin also recovered ZEA-induced steroidogenesis disorder by regulating steroidogenic enzyme gene and proteins (FSH-R, CYP19A1). Conclusions: Collectively, these findings show that isorhamnetin protects granulosa cells from ZEA-induced damage via the PI3K/Akt signaling pathway, which promotes proliferation, alleviates steroidogenesis disorder, ERS and oxidative stress.

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Section: Discussionsupporting

confidence: 53%

Isorhamnetin Protects Zearalenone-induced Damage via the PI3K/Akt Signaling Pathway in Porcine Granulosa Cells

Chen

Zhang

et al. 2021

Preprint

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“…To determine the involvement of ER stress in wogonoside-induced apoptosis of the AGS and MKN-45 cell lines, the activation of the ER stress pathway was determined. Compared with that in the control group the exposure to wogonoside significantly increased the protein and mRNA expression levels of CHOP, a known ER stress-related marker ( 21 ), and GRP78 and GPR94 ( Fig. 3A-F ), suggesting that ER stress was initiated by wogonoside treatment.…”

Section: Resultsmentioning

confidence: 88%

Wogonoside promotes apoptosis and ER stress in human gastric cancer cells by regulating the IRE1α pathway

Zhu

et al. 2021

Exp Ther Med

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Gastric cancer is a disease that occurs in the digestive system of humans and remains a problem in the medical field. Wogonoside, a natural flavonoid, has been reported to exert antitumor effects on various types of tumors. However, the effects of wogonoside on gastric cancer remain elusive. The aim of the present study was to detect whether wogonoside treatment could induce apoptosis and ER stress in gastric cancer cells. In the present study, CCK-8 assay was used to detect the cell viability, Annexin V/PI staining was used to detect the cells apoptosis, western blot analysis and real-time PCR analysis was used to detect the endoplasmic reticulum (ER) stress in the AGS and MKN-45 gastric cancer cell lines. Wogonoside treatment reduced the viability of AGS and MKN-45 cells and induced apoptosis. Furthermore, the expression level of caspase-3 and -9 significantly increased following wogonoside treatment compared with that in non-treated cells, and the protein expression levels of proapoptotic Bax and antiapoptotic Bcl-2 increased and decreased, respectively compared with that in the control group. In addition, the phosphorylated protein expression levels of mitogen-activated protein kinase kinase 5 (ASK1) and JNK increased following wogonoside treatment, and the protein expression levels of tumor necrosis factor receptor-associated factor 2 (TRAF2) and serine/threonine-protein kinase/endoribonuclease IRE1 (IRE1α) were also increased following treatment with 50 µM wogonoside for 48 h. Furthermore, the interactions between IRE1α, TRAF2 and ASK1 significantly increased following wogonoside treatment, suggesting that wogonoside induced endoplasmic reticulum (ER) stress in the AGS and MKN-45 cell lines. In addition, small interfering RNA-mediated silencing of IRE1α suppressed the activity of the IRE1α-TRAF2-ASK1 complex and prevented wogonoside-induced cell apoptosis. In conclusion, the results of the present study suggested that wogonoside exhibited antitumor activity by inducing ER stress-associated cell death through the IRE1α-TRAF2-ASK1 pathway.

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“…High concentrations of Ca 2+ can inhibit the synthesis of ATP by mitochondria. The lack of ATP would affect cell growth and even lead to apoptosis [ 34 ]. In addition, oxidative stress can also activate the cellular apoptosis induced by caspase-3 [ 35 ].…”

Section: Mt and Ovarian Functionsmentioning

confidence: 99%

Research progress of melatonin (MT) in improving ovarian function: a review of the current status

Guo

Sun

Wang

et al. 2021

Aging

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Melatonin (MT) is an endogenous hormone mainly synthesized by pineal cells, which has strong endogenous effects of eliminating free radicals and resisting oxidative damages. Melatonin (MT) can not only regulate the body’s seasonal and circadian rhythms; but also delay ovarian senescence, regulate ovarian biological rhythm, promote follicles formation, and improve oocyte quality and fertilization rate. This review aimd to provide evidence concerning the synthesis and distribution, ovarian function, and role of MT in development of follicles and oocytes. Moreover, the role of MT as antioxidative, participating in biological rhythm regulation, was also reviewed. Furthermore, the effects of MT on various ovarian related diseases were analyzed, particularly for the ovarian aging and polycystic ovary syndrome (PCOS).

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Melatonin protects mouse testes from palmitic acid‐induced lipotoxicity by attenuating oxidative stress and DNA damage in a SIRT1‐dependent manner

Cited by 139 publications

References 66 publications

Isorhamnetin Protects Zearalenone-induced Damage via the PI3K/Akt Signaling Pathway in Porcine Granulosa Cells

Isorhamnetin Protects Zearalenone-induced Damage via the PI3K/Akt Signaling Pathway in Porcine Granulosa Cells

Wogonoside promotes apoptosis and ER stress in human gastric cancer cells by regulating the IRE1α pathway

Research progress of melatonin (MT) in improving ovarian function: a review of the current status

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