Browsing by Subject "PKM2"

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    ENO3 regulates ferroptosis by interaction with PKM2 to promote the progression of metabolic dysfunction-associated steatotic liver disease
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2026) Qian Hao; Xue Li; Jing Liu; Minghao Li; Baoding Li; Shengjuan Hu; Yanling Li; Xiaofei Li; Yuanyuan Tang; Fuliang Pan; Yanxia Liu; Min Niu; Zhenzi Cao; Biología Celular e Histología
    Background. Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder characterized by excessive lipid accumulation in the liver. The glycolytic enzyme enolase 3 (ENO3) is reported to be most significantly elevated in the analysis of MASLD-related sequencing results based on the GEO database. However, the specific mechanism by which ENO3 regulates MASLD is not fully understood. Objective. To investigate the role and possible molecular mechanism of ENO3 in MASLD. Methods. The expression of ENO3 and PKM2 in the liver tissues of control and MASLD rats was detected by immunohistochemistry and western blot. In vitro studies involved treating THLE-2 cells with free fatty acids (FFA) and Ferrostatin-1 (Fer-1), as well as manipulating ENO3 expression via small interfering RNA (siRNA) and overexpression plasmids, and manipulating PKM2 expression via siRNA. Fat accumulation was assessed using Oil Red O staining and measurements of intracellular total cholesterol (TC) and triglycerides (TG). Ferroptosis markers, including SLC7A11, GPX4, Fe2+, and malondialdehyde (MDA), were evaluated. Protein-protein interactions between ENO3 and PKM2 were examined using co-immunoprecipitation (Co-IP) and immunofluorescence. Results. MASLD liver tissues exhibited significantly higher levels of ENO3 and PKM2. Silencing ENO3 in FFA-treated THLE-2 cells reduced fat accumulation, downregulated PKM2 expression, and decreased ferroptosis markers. Conversely, ENO3 overexpression promoted fat accumulation and ferroptosis, which were mitigated by Fer-1 or si-PKM2. Co-IP and immuno-fluorescence confirmed the physical interaction and co-localization of ENO3 and PKM2 in THLE-2 cells. Conclusions. ENO3 interacted with PKM2 to regulate ferroptosis and further promoted the progression of MASLD.
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    High expression of PKM2 as a poor prognosis indicator is associated with radiation resistance in cervical cancer
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2015) Zhao, Yajie; Shen, Liangfang; Chen, Xi; Qian, Yujie; Zhou, Qin; Wang, Ying; Li, Kai; Liu, Miaomiao; Zhang, Sai; Huang, Xinqiong
    Our study aimed to investigate the association of Pyruvate Kinase isozyme type M2 (PKM2) with radiation resistance in locally advanced cervical squamous cell carcinoma (LACSCC). We retros-pectively reviewed 132 female patients who received primary radiation therapy to treat LACSCC at Federation Internationale of Gynecologie and Obstetrigue（FIGO）stages IB-IVA. Forty-seven patients with progression free survival (PFS) of less than 36 months were regarded to have radiation resistance. Eighty-five patients with PFS no less than 36 months were regarded as radiation sensitive. Using immunohistochemistry, we found that the overexpression rate of PKM2 in radiation resistant and radiation sensitive patients was 87.2% and 57.6%, respectively, and the difference was statistically significant (p＜0.001). The 5-year progress free survival rates in patients with low and high expression of PKM2 was 80.4% and 60.5%, respectively, and the difference was statistically significant (p=0.008). Multivariate Cox regression analysis identified that high expression of PKM2 is an independent negative prognostic factor in cervical cancer patients [Hazard ratio (95% CI), 2.888 (1.347, 6.194) p=0.006]. These results demonstrate that overexpression of PKM2 contributes to radiation resistance and acts a poor prognosis indicator in patients with LACSCC.
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    The role and mechanism of PKM2 in the development of LPS-induced acute kidney injury
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Wu, Jiajun; Rong, Shu; Zhou, Jing; Yuan, Weijie
    A previous study suggested that pyruvate kinase M2 (PKM2) plays a vital role of metabolic reprogramming in the regulation of the innate inflammatory response, while PKM2 is a sensitive biomarker for nephrotoxicity. In this study, we investigated the role and mechanism of PKM2 in development of LPS-induced acute kidney injury. The AKI model of mice was established using LPS. The serum levels of blood urea nitrogen (Bun), creatinine (Cr), and Cystatin C (CysC) were identified using the enzyme-linked immunosorbent assay (ELISA). Hematoxylin and Eosin staining (H&E) was employed to assess pathological changes in kidney tissues of LPSinduced AKI model. Immunohistochemical staining and Western blot analysis were carried out to determine the expression of apoptosis-related factors at protein levels. We found that Bun, CysC, and Cr were significantly increased in the LPS group compared with the control group. The histopathological assay showed model swollen tubular epithelial cells and the presence of vacuolar degeneration in the LPS-induced AKI. In addition, expression levels of PKM2 significantly increased in the LPS group compared with the control group at both protein and mRNA levels (P<0.01). The inhibition of PKM2 by shikonin notably suppressed the expression of HIF-1α and apoptosis-related factors such as BNIP3, Bax, and Caspase-3, while the inhibition of PKM2 by shikonin significantly improved the histopathological symptoms of LPS-induced AKI. This study demonstrated the potential role of PKM2 in LPSinduced AKI and identified PKM2 as a promising therapeutic target in the treatment of AKI.