Pyrroloquinoline quinine protects HK-2 cells against high glucose-induced oxidative stress and apoptosis through Sirt3 and PI3K/Akt/FoxO3a signaling pathway

Wang, Ziqiang; Liu, Ying; Wang, Ying; Zhao, Kunxiao; Chi, Yue; Wang, Baoxing

doi:10.1016/j.bbrc.2018.11.140

Cited by 44 publications

(31 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Surprisingly, SIRT2 inhibition had no influence on the phosphorylated levels of FoxO3a. SIRT1 and SIRT3 are known to mediate FoxO3a phosphorylation via Akt [61,62]; here, SIRT2 did not seem to regulate the Akt-dependent FoxO3a phosphorylation pathways in oocytes. However, a second regulatory layer is FoxO acetylation by p300, CBP, and PCAF [63,64,65], followed by deacetylation by class I and II histone deacetylases, including SIRT1 [66,67].…”

Section: Discussionmentioning

confidence: 60%

SIRT2 Inhibition Results in Meiotic Arrest, Mitochondrial Dysfunction, and Disturbance of Redox Homeostasis during Bovine Oocyte Maturation

Jiang

et al. 2019

IJMS

View full text Add to dashboard Cite

SIRT2, a member of the sirtuin family, has been recently shown to exert important effects on mitosis and/or metabolism. However, its roles in oocyte maturation have not been fully clarified. In this study, SIRT2, located in the cytoplasm and nucleus, was found in abundance in the meiotic stage, and its expression gradually decreased until the blastocyst stage. Treatment with SIRT2 inhibitors resulted in the prevention of oocyte maturation and the formation of poor-quality oocytes. By performing confocal scanning and quantitative analysis, the results showed that SIRT2 inhibition induced prominent defects in spindle/chromosome morphology, and led to the hyperacetylation of α-tubulin and H4K16. In particular, SIRT2 inhibition impeded cytoplasmic maturation by disturbing the normal distribution of cortical granules, endoplasmic reticulum, and mitochondria during oocyte meiosis. Meanwhile, exposure to SirReal2 led to elevated intracellular reactive oxygen species (ROS) accumulation, low ATP production, and reduced mitochondrial membrane potential in oocytes. Further analysis revealed that SIRT2 inhibition modulated mitochondrial biogenesis and dynamics via the downregulation of TFAM and Mfn2, and the upregulation of DRP1. Mechanistically, SIRT2 inhibition blocked the nuclear translocation of FoxO3a by increasing FoxO3a acetylation, thereby downregulating the expression of FoxO3a-dependent antioxidant genes SOD2 and Cat. These results provide insights into the potential mechanisms by which SIRT2-dependent deacetylation activity exerts its effects on oocyte quality.

show abstract

Section: Discussionmentioning

confidence: 60%

SIRT2 Inhibition Results in Meiotic Arrest, Mitochondrial Dysfunction, and Disturbance of Redox Homeostasis during Bovine Oocyte Maturation

Jiang

et al. 2019

IJMS

View full text Add to dashboard Cite

show abstract

“…It is one of the key transcription factors regulating oxidative stress signaling pathway. For example, the antioxidant DMY can protect HUVECs from SNPinduced oxidative damage by activating the PI3K/Akt/FoxO3a signaling pathway (Zhang et al, 2019); PPQ can protect HK-2 from high glucose-induced oxidative damage and apoptosis through Sirt3 and PI3K/Akt/FoxO3a signaling pathways (Wang et al, 2018); and TSA protects myocardium from oxidative stress-mediated damage by increasing H4 acetylation in the FoxO3a promoter region as well as the expression of FoxO3a, MnSOD, and CAT (Guo et al, 2017). However, it has also been reported that FoxO3a can instead induce apoptosis under oxidative stress conditions in the body.…”

Section: Discussionmentioning

confidence: 99%

Effect of Transcriptional Regulatory Factor FoxO3a on Central Nervous System Oxygen Toxicity

Zhang¹,

You

Chen

et al. 2020

Front. Physiol.

View full text Add to dashboard Cite

Central nervous system (CNS) oxygen toxicity (CNS-OT) is a toxic reaction that appears after the inhalation of gas at an excessive oxygen partial pressure during underwater operation or hyperbaric oxygen (HBO) treatment. The mechanism of CNS-OT has not been clearly characterized. Though it has been attributed to the excessive oxidative stress induced by HBO, evidences against this hypothesis have been reported. Here we find that Forkhead box protein O3 (FoxO3a) is important for CNS-OT protection. FoxO3a knock-out (KO) mice had a shorter latency to develop convulsions and greater number of seizures within a certain period of time. The acute lung injury (ALI) induced by CNS-OT was also more severe in FoxO3a KO mice. Further analysis reveals a significant decrease in the activity of catalase (CAT), an antioxidant enzyme and a significant increase in the content of malondialdehyde (MDA), an oxidative product, in brain tissues of FoxO3a KO mice. Short-time HBO exposure could increase FoxO3a expression level and trigger its nuclear translocation. The level of nuclear localized FoxO3a peaked at 8 h after exposure. Our results demonstrate that the activity of FoxO3a is highly sensitive to HBO exposure and FoxO3a plays important roles in protecting CNS-OT. Further mechanic analysis reveals that FoxO3a protects CNS-OT via activating antioxidative signaling pathway.

show abstract

“…The PI3K pathway regulates the activation of primordial follicles via transcription factor FoxO3 [25][26][27], and it has been reported that PI3K inhibitor decreases the levels of phosphorylated FoxO3a (p-FoxO3a) while increasing the levels of nuclear FoxO3a [28]. The PI3K/AKT/FoxO3a pathway is involved in the regulation of various physiological processes via NO or NOS, guaranteeing an improved follicular microenvironment for developing oocytes and inhibiting granulosa cell apoptosis [29,30]. During the migration of endothelial cells, peroxisome proliferator-activated receptor coactivator 1α (PGC-1α) is downregulated by NO via the activation of the PI3K/protein kinase B (Akt protein) pathway and FoxO3a protein [31].…”

Section: Introductionmentioning

confidence: 99%

Nitric Oxide Synthase Is Involved in Follicular Development via the PI3K/AKT/FoxO3a Pathway in Neonatal and Immature Rats

Zhang

Zhu

et al. 2020

Animals

View full text Add to dashboard Cite

It is assumed that nitric oxide synthase and nitric oxide are involved in the regulation of female reproduction. This study aimed to assess the roles of nitric oxide synthase (NOS) in follicular development. The endothelial NOS (eNOS) inhibitor L-NAME, inducible NOS (iNOS) inhibitor S-Methylisothiourea (SMT) and NOS substrate L-arginine (L-Arg) were used in the NOS inhibition models in vivo. Neonatal female rats were treated with phosphate buffer saline (PBS, control), L-NAME (L-NG-Nitroarginine Methyl Ester, 40 mg/kg), SMT (S-Methylisothiourea, 10 mg/kg), L-NAME + SMT, or L-Arg (L-arginine, 50 mg/kg) via subcutaneous (SC) injection on a daily basis for 19 consecutive days, with the samples being collected on specific postnatal days (PD5, PD10, and PD19). The results indicated that the number of antral follicles, the activity of total-NOS, iNOS, neuronal NOS (nNOS), and eNOS, and the content of NO in the ovary were significantly (p < 0.05) increased in the L-Arg group at PD19, while those in L + S group were significantly (p < 0.05) decreased. Meanwhile, the ovarian expression in the L-Arg group in terms of p-AKT, p-FoxO3a, and LC3-II on PD19 were significantly (p < 0.05) upregulated, while the expressions of PTEN and cleaved Caspase-3 were (p < 0.05) downregulated as a result of NOS/NO generation, respectively. Therefore, the results suggest that NOS is possibly involved in the maturation of follicular development to puberty via the PI3K/AKT/FoxO3a pathway, through follicular autophagia and apoptosis mechanisms.

show abstract

Pyrroloquinoline quinine protects HK-2 cells against high glucose-induced oxidative stress and apoptosis through Sirt3 and PI3K/Akt/FoxO3a signaling pathway

Cited by 44 publications

References 22 publications

SIRT2 Inhibition Results in Meiotic Arrest, Mitochondrial Dysfunction, and Disturbance of Redox Homeostasis during Bovine Oocyte Maturation

SIRT2 Inhibition Results in Meiotic Arrest, Mitochondrial Dysfunction, and Disturbance of Redox Homeostasis during Bovine Oocyte Maturation

Effect of Transcriptional Regulatory Factor FoxO3a on Central Nervous System Oxygen Toxicity

Nitric Oxide Synthase Is Involved in Follicular Development via the PI3K/AKT/FoxO3a Pathway in Neonatal and Immature Rats

Contact Info

Product

Resources

About

Pyrroloquinoline quinine protects HK-2 cells against high glucose-induced oxidative stress and apoptosis through Sirt3 and PI3K/Akt/FoxO3a signaling pathway

Cited by 44 publications

References 22 publications

SIRT2 Inhibition Results in Meiotic Arrest, Mitochondrial Dysfunction, and Disturbance of Redox Homeostasis during Bovine Oocyte Maturation

SIRT2 Inhibition Results in Meiotic Arrest, Mitochondrial Dysfunction, and Disturbance of Redox Homeostasis during Bovine Oocyte Maturation

Effect of Transcriptional Regulatory Factor FoxO3a on Central Nervous System Oxygen Toxicity

Nitric Oxide Synthase Is Involved in Follicular Development via the PI3K/AKT/FoxO3a Pathway in Neonatal and Immature Rats

Contact Info

Product

Resources

About

Pyrroloquinoline quinine protects HK-2 cells against high glucose-induced oxidative stress and apoptosis through Sirt3 and PI3K/Akt/FoxO3a signaling pathway