Itaconate regulates the glycolysis/pentose phosphate pathway transition to maintain boar sperm linear motility by regulating redox homeostasis

Zhu, Zhendong; Umehara, Takashi; Tsujita, Natsumi; Kawai, Tomoko; Goto, Masaaki; Cheng, Bo; Shimada, M.

doi:10.1016/j.freeradbiomed.2020.07.008

Cited by 29 publications

(27 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A growing number of evidences have revealed that metabolic intermediates are involved in many physical and pathological processes, including the regulation of inflammatory response, oxidative stress, and cancers. As a metabolite from the tricarboxylic acid cycle, OI was recently found to have a strong anti-inflammatory property, regulating redox homeostasis, and showed a protective effect in many pathologies ( Mills et al, 2018 ; Li Y. et al, 2020 ; Zhu et al, 2020 ). In a recent study, OI showed a protective effect in the liver ischemia-reperfusion injury mouse model by activating the Nrf2 pathway ( Yi Z. et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

4-OI Attenuates Carbon Tetrachloride-Induced Hepatic Injury via Regulating Oxidative Stress and the Inflammatory Response

Yang

Yin

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

The liver is an important metabolic organ, and acute liver injury (ALI) is potentially lethal. Itaconate, a metabolic intermediate from the tricarboxylic acid cycle, showed emerging anti-oxidative and anti-inflammation properties, and an accumulating protective effect in multiple diseases, but its role in ALI still needs to be further explored. Here we established an ALI model induced by carbon tetrachloride in mice. Our results showed that 4-Octyl itaconate (OI), a derivate of itaconate, mitigated hepatic damage by improving liver function, reducing histopathological damage, and decreasing the death of hepatocytes. Additionally, OI decreased myeloperoxidase and thiobarbituric acid reactive substances (TBARS) levels in the ALI model. OI also inhibited the inflammatory response by reducing pro-inflammatory cytokine secretion (IL-6, TNF-α, IL-1β, and MCP-1) and infiltration of macrophages and neutrophils in the ALI model. However, administration of ML385, a specified Nrf2 inhibitor, eliminated the protective properties of OI in the CCl4-induced liver injury model by increasing hepatic damage and oxidative stress. Furthermore, OI increased the expression and nuclear translocation of Nrf2 and elevated the expression of heme oxygenase-1 and NAD(P)H quinone oxidoreductase 1, while knockdown of Nrf2 eliminated these effects in murine hepatocyte NCTC 1469 under CCl4 treatment. Moreover, we found that OI reduced serum High-mobility group box 1 (HMGB1) levels in CCl4-treated mice. Finally, OI inhibited nuclear translocation of factor-kappa B (NF-𝜅B) and inflammatory cytokine production in murine macrophages. In conclusion, these results indicated that OI ameliorated CCl4-induced ALI by mitigating oxidative stress and the inflammatory response. The possible mechanism was associated with the elevation of Nrf2 nuclear translocation and inhibition of HMGB1 mediated the nuclear translocation of NF-𝜅B.

show abstract

Section: Discussionmentioning

confidence: 99%

4-OI Attenuates Carbon Tetrachloride-Induced Hepatic Injury via Regulating Oxidative Stress and the Inflammatory Response

Yang

Yin

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Reactive oxygen species (ROS) have physiologically relevant roles in improving intracellular cAMP levels, acrosome reactions, hyperactivation and spermatozoa fusion [10][11][12]. Uncontrolled (i.e.…”

Section: Introductionmentioning

confidence: 99%

Freeze-thawing impairs the motility, plasma membrane integrity and mitochondria function of boar spermatozoa through generating excessive ROS

Zhang

Wang

et al. 2021

BMC Vet Res

View full text Add to dashboard Cite

Background Cryopreservation is an efficient way to store spermatozoa and is closely associated with the quality of sperm after the freeze-thaw process. During freeze-thaw cycling, excessive reactive oxygen species (ROS) are produced, and the effects of ROS on boar sperm during cryopreservation have not been identified. Results In this study, we evaluated the quality of boar spermatozoa in different steps of cryopreservation (extension, cooling, and thawing for 30 min and 240 min) with or without boar-sperm antioxidant (N-acetylcysteine (NAC)). The ROS levels, sperm motility, plasma membrane integrity, mitochondrial activity, sperm chromatin structure, ATP content, and sperm apoptosis were assayed. After thawing, the ROS level and sperm apoptosis were significantly increased, and the sperm motility, plasma membrane integrity, mitochondrial activity, sperm chromatin structure, and ATP content were significantly impaired compared with those at the extension period and cooling period. Moreover, the addition of N-acetyl L-cysteine (NAC) reversed these changes. Conclusion The freeze-thawing of boar spermatozoa impaired their motility, plasma membrane, mitochondrial activity, sperm chromatin structure and apoptosis by producing excessive ROS. Thus, the downregulation of ROS level by antioxidants, especially the NAC, is important for manufacturing frozen pig sperm to increase reproductive cells and livestock propagation, as well as to improve the application of frozen semen in pigs worldwide.

show abstract

“…Remarkably, in boar sperm, it was reported that a decreased glucose level in extender‐induced linear motility boosted OXPHOS, whereas complete removal of glucose from the medium failed to maintain linear sperm motility and mitochondrial activity 10 . Glucose is used as a substrate not only in glycolysis, but also in the pentose phosphate pathway to generate NADPH, which affects redox homeostasis and is essential to maintain sperm motility 15,16 . This suggests that pyruvate, which is derived from glucose, is not the main source of acetyl CoA to activate OXPHOS in sperm.…”

Section: Introductionmentioning

confidence: 99%

Saturated fatty acids accelerate linear motility through mitochondrial ATP production in bull sperm

Islam

Umehara

Tsujita

et al. 2021

Reprod Medicine & Biology

Self Cite

View full text Add to dashboard Cite

Purpose The present study was undertaken to clarify whether bovine sperm could take up fatty acids (FAs) and produce ATP to maintain linear motility. Methods Frozen bovine semen was thawed in media containing either lipid mixture (LM) or FAs, and sperm motility was analyzed. The kinetic changes in FA levels in sperm were detected using gas chromatography‐mass spectrometry. The mitochondrial activity of sperm thawed in media containing LM or FAs was analyzed based on the fluorescence intensity of JC‐1 staining and the oxygen consumption rate. FA transporters were observed using whole‐mounted immunofluorescence. Results Sperm linear motility was significantly (P < .05) increased after thawing in media with LM and FA. Moreover, saturated fatty acids were predominant in sperm thawed in media with LM. Notably, our study revealed that frozen bovine sperm possessed FA transporters in the midpiece where the fluorescence signals were detected after treatment with fluorescence‐tagged FA. Treatment with FA activated electron transport in mitochondria through β‐oxidation. Conclusions Sperm linear motility is facilitated by FAs in the thawing media used for frozen bovine sperm. This might provide a new approach for upgrading the artificial insemination technique used in both livestock animals and human infertility care.

show abstract

Itaconate regulates the glycolysis/pentose phosphate pathway transition to maintain boar sperm linear motility by regulating redox homeostasis

Cited by 29 publications

References 47 publications

4-OI Attenuates Carbon Tetrachloride-Induced Hepatic Injury via Regulating Oxidative Stress and the Inflammatory Response

4-OI Attenuates Carbon Tetrachloride-Induced Hepatic Injury via Regulating Oxidative Stress and the Inflammatory Response

Freeze-thawing impairs the motility, plasma membrane integrity and mitochondria function of boar spermatozoa through generating excessive ROS

Saturated fatty acids accelerate linear motility through mitochondrial ATP production in bull sperm

Contact Info

Product

Resources

About