INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Lin Xu,Baoju Wang,Zhenbo Gang,Zhibin Han,Aowen Wang,Qi Liu,Hongyang Liu,Shilong Wei,Zhiguo Lin,Chuncheng Xie,Li Hu
Background Glioblastoma (GBM) is an aggressive cancer with limited therapeutic options. Investigating the mechanisms underlying temozolomide (TMZ) resistance and enhancing its sensitivity remain critical for improving GBM treatment outcomes. Ubiquitin-conjugating enzyme E2S (UBE2S) has been implicated in various cancers; however, its role in TMZ resistance in GBM remains unclear. Methods After UBE2S knockdown, cell viability, apoptosis, and DNA damage were measured in TMZ-treated GBM cells. Immunoprecipitation coupled with mass spectrometry was employed to identify a protein complex involving UBE2S and phosphoglycerate mutase 1 (PGAM1). Co-immunoprecipitation and ubiquitination assays were conducted to examine the interactions among UBE2S, PGAM1, and Otubain-2 (OTUB2). In vivo, a GBM mouse model was used to evaluate the impact of UBE2S knockdown on TMZ efficacy. Results UBE2S was found to be overexpressed in GBM cells, where it interacts with PGAM1 and OTUB2 to inhibit PGAM1 degradation via K48-linked deubiquitylation. This interaction increased PGAM1 protein levels, promoting DNA repair and reducing apoptosis, thereby decreasing the sensitivity of GBM cells to TMZ. Conclusion UBE2S plays a critical role in TMZ resistance by stabilizing PGAM1 protein levels through its interaction with OTUB2. Targeting UBE2S represents a promising therapeutic strategy to enhance TMZ efficacy and overcome chemotherapy resistance in GBM.
研究领域:
肿瘤学
·
分子生物学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
·
2026
·Vol. 40
·期 8
·e71024
·
IF 3.6
Xueru Wang,Na Luo,Yonggang Ma,Hui Zou,Xishuai Tong,Jiaqiao Zhu,Ruilong Song,Hongyan Zhao,Zongping Liu
Cadmium (Cd) is a widespread environmental contaminant that impairs male reproductive function; however, the metabolic mechanisms underlying Cd‐induced testicular toxicity remain incompletely understood. This study investigated whether serine supplementation could alleviate Cd‐induced testicular injury and explored its association with phosphoglycerate mutase 1 (PGAM1)‐ and phosphoglycerate dehydrogenase (PHGDH)‐related serine metabolism. Forty male C57BL/6 mice were randomly assigned to four groups and received ultrapure water, serine (50 g/L), Cd (50 mg/L), or Cd plus serine in drinking water for 18 weeks. Testicular morphology, hormone levels, ion homeostasis, oxidative stress, inflammation, glycolytic metabolism, fibrosis, apoptosis, and the expression of PGAM1/PHGDH‐related proteins were evaluated. Cd exposure induced marked testicular injury, characterized by reduced testicular weight and index, disrupted reproductive hormone levels, histopathological damage, ion imbalance, oxidative stress, inflammatory responses, and decreased expression of blood–testis barrier‐associated proteins. Cd also suppressed glycolysis and serine biosynthesis, as evidenced by reduced activities of glycolytic enzymes, decreased lactate and pyruvate production, lower serine levels, inhibited PHGDH, PSAT1, and PSPH expression, and altered PGAM1 expression. These changes were accompanied by increased fibrosis and germ cell apoptosis. Serine supplementation substantially ameliorated these abnormalities, restoring metabolic homeostasis, improving antioxidant capacity, reducing inflammation, and attenuating fibrosis and apoptosis. In conclusion, serine exerts a strong protective effect against Cd‐induced male reproductive toxicity by counteracting metabolic dyshomeostasis, highlighting its potential therapeutic value as a beneficial additive against heavy metal‐associated reproductive damage. Serine mitigates cadmium‐induced testicular injury in mice by inhibiting the PGAM1/PHGDH pathway, restoring ion homeostasis and glycolysis, and relieving oxidative stress, inflammation, fibrosis, and apoptosis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）