Effects of quercetin on rat testis aerobic glycolysis

Trejo, Raquel; Valadéz-Salazar, Alicia; Delhumeau, Graciela

doi:10.1139/y95-722

Cited by 21 publications

(7 citation statements)

References 30 publications

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“…Interestingly, our results showed quercetin could block GF-triggered increase of aerobic glycolysis. Quercetin has been reported to inhibit aerobic glycolysis levels in rat testis and some tumor cells (30,31). Our results further proved quercetin played as an inhibitor of aerobic glycolysis in a cell model of GF-induce renal injury.…”

Section: Discussionsupporting

confidence: 75%

Quercetin Antagonizes Glucose Fluctuation Induced Renal Injury by Inhibiting Aerobic Glycolysis via HIF-1α/miR-210/ISCU/FeS Pathway

Liu

et al. 2021

Front. Med.

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Background and Objective: Glucose fluctuation (GF) has been reported to induce renal injury and diabetic nephropathy (DN). However, the mechanism still remains ambiguous. Mitochondrial energy metabolism, especially aerobic glycolysis, has been a hotspot of DN research for decades. The activation of HIF-1α/miR210/ISCU/FeS axis has provided a new explanation for aerobic glycolysis. Our previous studies indicated quercetin as a potential therapeutic drug for DN. This study aims to evaluate levels of aerobic glycolysis and repressive effect of quercetin via HIF-1α/miR210/ISCU/FeS axis in a cell model of GF.Methods: The mouse glomerular mesangial cells (MCs) were exposed in high or oscillating glucose with or without quercetin treatment. Cell viability was measured by CCK8 assay. Aerobic glycolysis flux was evaluated by lactate acid, pH activity of PFK. Apoptosis level was confirmed by Annexin V-APC/7-AAD double staining and activity of caspase-3. TNF-α and IL-1β were used to evaluate inflammation levels.Results: GF deteriorated inflammation damage and apoptosis injury in MCs, while quercetin could alleviate this GF-triggered cytotoxicity. GF intensified aerobic glycolysis in MCs and quercetin could inhibit this intensification in a dose-dependent manner. Quercetin prevented activities of two FeS-dependent metabolic enzymes, aconitase, and complex I, under GF injury in MCs. The mRNA expression and protein contents of HIF-1α were increased after GF exposure, and these could be alleviated by quercetin treatment. Knockdown of ISCU by siRNA and Up-regulating of miR-210 by mimic could weaken the effects of quercetin that maintained protein levels of ISCU1/2, improved cell viability, relieved inflammation injury, decreased apoptosis, and reduced aerobic glycolysis switch in MCs.Conclusion: Quercetin antagonizes GF-induced renal injury by suppressing aerobic glycolysis via HIF-1α/miR-210/ISCU/FeS pathway in MCs cell model. Our findings contribute to a new insight into understanding the mechanism of GF-induced renal injury and protective effects of quercetin.

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Section: Discussionsupporting

confidence: 75%

Quercetin Antagonizes Glucose Fluctuation Induced Renal Injury by Inhibiting Aerobic Glycolysis via HIF-1α/miR-210/ISCU/FeS Pathway

Liu

et al. 2021

Front. Med.

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“…Supportive of this notion is the demonstration that these other nondying cell types, such as Sertoli cells and spermatogonia, are known to use glycolysis for their energy production (whereas the dying cell types prefer OXPHOS; see Refs. 3,28,45,53,64). Of note, when using OXPHOS inhibitors, we cannot exclude the possibility that the ATP decrease would occur in different cells than the death process.…”

Section: Discussionmentioning

confidence: 99%

“…Spermatogonia, mature spermatozoa, and the somatic Sertoli cells exhibit high glycolytic activity, whereas spermatocytes and spermatids produce ATP mainly by mitochondrial oxidative phosphorylation (OXPHOS; see Refs. 3,28,31,37,45,53,64). Interestingly, the cell types that use OXPHOS for energy production (i.e., spermatids and spermatocytes) are sensitive to death-inducing signals such as hormonal deprivation, Fas activation, and elevated temperature (19,24,34,47,48,51,60,60).…”

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confidence: 99%

Regulation of human male germ cell death by modulators of ATP production

Erkkilä¹,

Kyttänen²,

Wikström³

et al. 2006

American Journal of Physiology-Endocrinology and Metabolism

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The understanding of testicular physiology, pathology, and male fertility issues requires knowledge of male germ cell death and energy production. Here, we induced human male germ cell apoptosis (detected by Southern blot analysis of DNA fragmentation, TUNEL, activation of caspases-3 and -9, and electron microscopy) by incubating seminiferous tubule segments under hormone-and serum-free conditions. Inhibitors of complexes I to IV of mitochondrial respiration, exposure to anoxia, and inhibition of F0F1-ATPase (with oligomycin) decreased the ATP levels (analyzed by HPLC) and suppressed apoptosis at 4 h. Uncoupler 2,4-dinitrophenol (DNP) and oligomycin combination also suppressed death at 4 h, as did the DNP alone. Inhibition of glycolysis by 2-deoxyglucose neither suppressed nor further induced apoptosis nor altered the antiapoptotic effects of the mitochondrial inhibitors. Furthermore, Fas system activation did not modify the effects of mitochondrial modulators. After 24 h, delayed male germ cell apoptosis was observed despite the presence of the mitochondrial inhibitors. We conclude that the mitochondrial ATP production machinery plays an important role in regulating in vitroinduced primary pathways of human male germ apoptosis. The ATP synthesized by the F0F1-ATPase seems to be the crucial death regulator, rather than any of the complexes (I-IV) alone, the functional electron transport chain, or the membrane potential. We also conclude that there seem to be secondary pathways of human testicular cell apoptosis that do not require mitochondrial ATP production. The present study emphasizes the role of the main catabolic pathways in the complex network of regulating events of male germ cell life and death.testis; spermatogenesis; apoptosis; mitochondria; oxidative phosphorylation THE ENERGY METABOLISM and catabolism in the testis involve a unique network of reactions and include several testis-specific enzymes, hormonal regulation, and essential cell-to-cell interactions (1,8,27,29,41,43,55,56,58). The proper functioning of this network is critical for testicular physiology. Another crucial regulator of normal testicular function is appropriate germ cell death, and the disruption of this orderly process is associated with several male reproductive disorders (15,16,30,38,47,54,60). How these two entities, i.e., energy metabolism/catabolism and male germ cell death, are linked is presently unclear.The cell types of the seminiferous epithelium differ from each other in their sensitivity to death-inducing signals and with their preferred substrates for energy metabolism. Spermatogonia, mature spermatozoa, and the somatic Sertoli cells exhibit high glycolytic activity, whereas spermatocytes and spermatids produce ATP mainly by mitochondrial oxidative phosphorylation (OXPHOS; see Refs. 3,28,31,37,45,53,64). Interestingly, the cell types that use OXPHOS for energy production (i.e., spermatids and spermatocytes) are sensitive to death-inducing signals such as hormonal deprivation, Fas activation, and elevated temperature ...

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“…ATP is synthesized by most of the spermatid through the degradation of lactate and pyruvate produced massively by Sertoli cells (Robinson and Fritz, 1981;Grootegoed et al, 1984). Pharmacological lactate deprivation induces cell death in isolated rat germ cells (Trejo et al, 1995). Erkkila et al (2002) reported that testicular cell death was effectively regulated by lactate, which may be regarded as a potential compound for optimizing in vitro methods involving male germ cells for assisted reproduction.…”

Section: Introductionmentioning

confidence: 99%