Protein palmitoylation-mediated palmitic acid sensing causes blood-testis barrier damage via inducing ER stress

Ge, Xie; He, Zhaowanyue; Cao, Chun; Xue, Tongmin; Jing, Jun; Ma, Rujun; Wei, Zhao; Liu, Ling; Jueraitetibaike, Kadiliya; Ma, Jinzhao; Feng, Yuming; Zhang, Qian; Zou, Zhichuan; Chen, Li; Fu, Cuizhang; Song, Ninghong; Yao, Bing

doi:10.1016/j.redox.2022.102380

Cited by 23 publications

(13 citation statements)

References 73 publications

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“…Palmitoylation of proteins was analyzed using acyl-biotin exchange (ABE) assays as previously described, with some modifications ( 49 , 50 ). SUNE-1 cells treated with MGH-CP1 (S9735, Selleck) or transiently expressing Myc-tagged wild-type or palmitoylation-deficient (C335S, C367A) TEAD4 were subjected to ABE assay.…”

Section: Methodsmentioning

confidence: 99%

TEAD4 is a master regulator of high-risk nasopharyngeal carcinoma

Wang

Wei

et al. 2023

Sci. Adv.

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The molecular basis underlying nasopharyngeal carcinoma (NPC) remains unclear. Recent progress in transcriptional regulatory network analysis helps identify the master regulator (MR) proteins that transcriptionally define malignant tumor phenotypes. Here, we investigated transcription factor-target interactions and identified TEA domain transcription factor 4 (TEAD4) as an MR of high-risk NPC. Precisely, TEAD4 promoted NPC migration, invasion and cisplatin resistance, depending on its autopalmitoylation. Mechanistically, YTHDF2 (YTH domain family 2) recognized WTAP (Wilms tumor 1–associating protein)–mediated TEAD4 m 6 A methylation to facilitate its stability and led to aberrant up-regulation of TEAD4. Up-regulated TEAD4 further drove NPC progression by transcriptionally activating BZW2 (basic leucine zipper and W2 domains 2) to induce the oncogenic AKT pathway. Moreover, the transcriptional activity of TEAD4 was independent of its canonical coactivators YAP/TAZ. Clinically, TEAD4 serves as an independent predictor of unfavorable prognosis and cisplatin response in NPC. Our data revealed the crucial role of TEAD4 in driving tumor malignancy, thus, may provide therapeutic vulnerability in NPC.

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Section: Methodsmentioning

confidence: 99%

TEAD4 is a master regulator of high-risk nasopharyngeal carcinoma

Wang

Wei

et al. 2023

Sci. Adv.

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“…Thus, the appropriate dosage of n-3 PUFAs needs to be determined. According to the previous research in our lab, 10 to 200 µM n-3 PUFAs have been used [ 26 , 27 ]. In this study, we constructed a mouse PCOS model and found that the addition of 50 µM n-3 PUFAs could significantly increase the maturation rate of the oocytes from PCOS mice via IVM culture ( P < 0.05), suggesting that the supplementation of n-3 PUFA in vitro culture medium could also improve oocyte quality in PCOS mice.…”

Section: Discussionmentioning

confidence: 99%

Effects of n-3 PUFA supplementation on oocyte in vitro maturation in mice with polycystic ovary syndrome

Wang

Xue

et al. 2023

J Ovarian Res

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Abstractn-3 PUFAs are classic antioxidant that can be used to treat follicular dysplasia and hyperinsulinemia caused by excessive oxidative stress in PCOS women. To investigate the effect of n-3 PUFA supplementation on the oocyte quality of polycystic ovary syndrome (PCOS) mice during in vitro maturation, a PCOS mouse model was established by dehydroepiandrosterone (DHEA). The GV oocytes of the control and PCOS groups were collected and cultured in vitro with or without n-3 PUFAs. After 14 h, the oocytes were collected. Our data demonstrated that the oocyte maturation rate of PCOS mice significantly increased after the addition of 50 µM n-3 PUFAs. The results of immunofluorescence showed that the abnormal rates of spindles and chromosomes in the PCOS + n-3 PUFA group were lower than those in the PCOS group. The mRNA expression of an antioxidant-related gene (Sirt1) and DNA damage repair genes (Brca1/Msh2) was found to be significantly rescued after n-3 treatment. Additionally, the results of living cell staining showed that the addition of n-3 PUFAs could reduce the levels of reactive oxygen species and mitochondrial superoxide in PCOS oocytes. In conclusion, the addition of 50 µM n-3 PUFAs during the in vitro maturation of PCOS mouse oocytes can improve the maturation rate by reducing the level of oxidative stress and the rate of spindle/chromosome abnormalities, providing valuable support during the IVM process.

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“…We performed metabolomics analysis on the related substances of the three major energy metabolites in cells. In the process of spermatogenesis, SCs only use a small part of glucose to meet their own energy needs but convert most of the glucose into lactate, which is used for the GC energy supply ( 21 ). In the present study, we found that most of the metabolome features detected for the glucose metabolism pathway, such as pyruvate and lactate, were not significantly changed in PA-treated SCs.…”

Section: Discussionmentioning

confidence: 99%

Atlas of metabolism reveals palmitic acid results in mitochondrial dysfunction and cell apoptosis by inhibiting fatty acid β-oxidation in Sertoli cells

Luo²,

Xuan³

et al. 2022

Front. Endocrinol.

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In recent years, the impact of lipotoxicity on male fertility has received extensive attention, especially on Sertoli cells (SCs). In SCs, energy metabolism is important as disorders of energy metabolism result in infertility eventually. However, the underlying mechanism of lipotoxicity on energy metabolism in SCs remains unknown. Advances in high-throughput metabolomics and lipidomics measurement platforms provide powerful tools to gain insights into complex biological systems. Here, we aimed to explore the potential molecular mechanisms of palmitic acid (PA) regulating energy metabolism in SCs based on metabolomics and lipidomics. The results showed that glucose metabolism-related metabolites were not significantly changed, which suggested that PA treatment had little effect on glucose metabolism and may not influence the normal energy supply from SCs to germ cells. However, fatty acid β-oxidation was inhibited according to accumulation of medium- and long-chain acylcarnitines in cells. In addition, the pool of amino acids and the levels of most individual amino acids involved in the tricarboxylic acid (TCA) cycle were not changed after PA treatment in SCs. Moreover, PA treatment of SCs significantly altered the lipidome, including significant decreases in cardiolipin and glycolipids as well as remarkable increases in ceramide and lysophospholipids, which indicated that mitochondrial function was affected and apoptosis was triggered. The increased apoptosis rate of SCs was verified by elevated protein expression levels of Cleaved Caspase-3 and Bax as well as decreased Bcl-2 protein expression level. Together, these findings indicated that PA may result in mitochondrial dysfunction and increased apoptosis by inhibiting fatty acid β-oxidation of SCs.

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Protein palmitoylation-mediated palmitic acid sensing causes blood-testis barrier damage via inducing ER stress

Cited by 23 publications

References 73 publications

TEAD4 is a master regulator of high-risk nasopharyngeal carcinoma

TEAD4 is a master regulator of high-risk nasopharyngeal carcinoma

Effects of n-3 PUFA supplementation on oocyte in vitro maturation in mice with polycystic ovary syndrome

Atlas of metabolism reveals palmitic acid results in mitochondrial dysfunction and cell apoptosis by inhibiting fatty acid β-oxidation in Sertoli cells

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