The FASEB Journal最新文献

{"title":"Correction to “Repeated sprint training in hypoxia induces specific skeletal muscle adaptations through S100A protein signaling”","authors":"","doi":"10.1096/fj.202500601","DOIUrl":"https://doi.org/10.1096/fj.202500601","url":null,"abstract":"<p>\u0000 <span>Lanfranchi, C.</span>, <span>Willis, S.J.</span>, <span>Laramée, L.</span>, <span>Conde Alonso, S.</span>, <span>Pialoux, V.</span>, <span>Kayser, B.</span>, <span>Millet, G.P.</span>, <span>Place, N.</span>, <span>Zanou, N.</span>, <span>2024</span>. <span>Repeated sprint training in hypoxia induces specific skeletal muscle adaptations through S100A protein signaling</span>. <i>The FASEB Journal</i> <span>38</span>(<span>8</span>): e23615, Doi: 10.1096/fj.202302084RR.\u0000 </p><p>Authors requested the correction to Figure 2.</p><p>In Figure 2 of the original manuscript, Panels E and F have been inverted and should be now represented as in the revised Figure 2. No other modification in the text is needed.</p><p>The corrected Figure 2 is as follows:</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202500601","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143535811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Angiopoietin-2 regulates the phenotypic switch of vascular smooth muscle cells","authors":"Xiaowen Gan,&nbsp;Shenjiao Lu,&nbsp;Fen Ning,&nbsp;Yixin Ye,&nbsp;Kaimin Guo,&nbsp;Miaojuan Chen,&nbsp;Deqiong Ou,&nbsp;Qinsheng Lu,&nbsp;Gendie E. Lash","doi":"10.1096/fj.202402754R","DOIUrl":"https://doi.org/10.1096/fj.202402754R","url":null,"abstract":"<p>During uterine spiral artery remodeling, vascular smooth muscle cells (VSMCs) become disorganized and undergo phenotypic switching from a contractile to a more synthetic phenotype. We have previously reported that uterine natural killer cells induce this VSMC phenotypic switching by secreting angiopoietin-2 (Ang-2). Here, we identified the specific mechanisms by which Ang-2 plays a role in this phenomenon. VSMCs isolated from human umbilical arteries were used as an in vitro model to investigate the role of Ang-2 in phenotypic switching. Human decidua tissue from preeclamptic and control pregnancies was collected to compare the expression levels of related proteins. Ang-2 induced a more synthetic phenotype in VSMCs as evidenced by decreased contractile marker expression, increased proliferation and migration, and an altered cytoskeleton. VSMC expressed integrin β6 interacted directly with Ang-2 and induced phosphorylation of FAK (S910 and Y397), AKT (S473), and mTOR (S2448). Knockdown of FAK recovered the calponin loss induced by Ang-2 and resulted in lower EZH2 abundance. Inhibition of FAK and EZH2 both attenuated Ang-2-induced inhibition of the LC3 II/LC3 I ratio and ATG7 expression, and proliferation. Lipid peroxidation inhibition by ferrostatin-1 or the IL-8 receptor antagonist navarixin inhibited the Ang-2-induced migration. IL-8 secretion was significantly lower with lipid peroxidation inhibition. In preeclamptic decidua, there were more unremodeled spiral arteries, and the abundance of Ang-2 was dysregulated. Ang-2 dysregulation may disrupt spiral artery remodeling and contribute to preeclampsia. Ang-2 may be a novel therapeutic target for the treatment of pregnancy complications affected by incomplete spiral artery remodeling.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial endogenous CSE/H2S inhibits endothelial pyroptosis by activating sirtuin1 to attenuate LPS-induced acute lung injury","authors":"Min Zhu,&nbsp;Xiaofang Fan,&nbsp;Nan Zhang,&nbsp;Hui Wang,&nbsp;Jianshe Ma,&nbsp;Xianghong Yin,&nbsp;Junyan Cai,&nbsp;Linjing Cong,&nbsp;Ran Chen,&nbsp;Junming Fan,&nbsp;Xiaoxia Kong,&nbsp;Bin Geng,&nbsp;Yongsheng Gong,&nbsp;Congkuo Du","doi":"10.1096/fj.202402042R","DOIUrl":"https://doi.org/10.1096/fj.202402042R","url":null,"abstract":"<p>Endothelial pyroptosis, a pro-inflammatory programmed cell death, promotes endothelial inflammation and is a pivotal process in the initial stage of acute lung injury (ALI). Hydrogen sulfide (H₂S), a gasotransmitter primarily dependent on cystathionine γ-lyase (CSE) in the cardiovascular and respiratory systems, plays a protective role during ALI. Nonetheless, the modulatory role and precise molecular mechanism of endothelial endogenous CSE/H₂S in the pathogenesis of ALI remain elusive. Herein, we prepared an ALI mouse model using intratracheal administration of LPS (5 mg/kg), and lung injury was assessed by evaluating pulmonary edema, inflammatory response, and endothelial pyroptosis. In this model, H₂S production from pulmonary tissues declined in a time-dependent manner, accompanied by a compensatory elevation of CSE protein levels. Treatment with the H₂S donor (NaHS) attenuated pulmonary edema, inflammatory cell infiltration, endothelial pyroptosis, and reduced serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Meanwhile, the inducible deletion of CSE in endothelial cells exacerbated these changes. The blocking effect of CSE/H₂S on endothelial pyroptosis (evidenced by caspase-11 activation and GSDMD-NT formation) was also confirmed in cultured pulmonary microvascular endothelial cells (PMECs). Mechanistically, H₂S-mediated regulation of sirtuin-1 (SIRT1) expression and activation (via sulfhydration) contributed to the modulatory process. Collectively, we uncovered that endothelial endogenous CSE/H₂S alleviates endothelial pyroptosis by activating SIRT1, thereby preventing LPS-induced acute lung injury.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Construction of competitive endogenous RNA network and identification of potential regulatory axis in vascular calcification” Xu, T, Li, Y, Cheng, M, et al. Construction of competitive endogenous RNA network and identification of potential regulatory axis in vascular calcification. FASEB J. 2024 Oct 31; 38(20):e70114. doi: 10.1096/fj.202400973RR","authors":"","doi":"10.1096/fj.202500586","DOIUrl":"https://doi.org/10.1096/fj.202500586","url":null,"abstract":"<p>In the original publication of the article, the authors checked the results and found a mistake in Figure 7B. The DAPI panel in the N group of original Figure 7B did not align with the merged panel in the group. Hence, they updated the figure. The DAPI panel in the revised figure 7B aligns with the merged panel.</p><p>The authors apologize for this error.</p><p>The corrected Figure 7 is as follows:</p><p><b>Figure 7</b> miR-145-5p overexpression inhibits VSMC calcification. (A) qRT-PCR analysis of Smad3 and miR-145-5p expression in VSMCs between normal and high phosphorus group; normalized by GAPDH or U6 respectively, *<i>p</i> &lt; .05. (B) Immunofluorescence staining for Smad3 in VSMCs untreated or treated with β-GP. DAPI, staining for nucleus. Scale bars: 20 μm. (C,D) Alizarin red S staining in β-GP treated VSMC transferred with miR-145-5p mimic or miR-145-5p inhibitor compared with β-GP + NC1 or β-GP + NC2, *<i>p</i> &lt; .05. (E,F) Western blot analyses of Smad3, osteoblast-specific marker (OPN), VSMC-specific marker (22α) in miR-145-5p mimic group or miR-145-5p inhibitor group compared with negative control group (β-GP + NC1; β-GP + NC2), *<i>p</i> &lt; 0.05. (G) qRT-PCR analysis of Smad3 expression after transfection of miR-145-5p mimic or miR-145-5p inhibitor in high phosphorus model; compared with negative control group (β-GP + NC1; β-GP + NC2), *<i>p</i> &lt; .05. (H) Sequence of the 3 -UTR of Smad3 mRNA that matches the miR-145-5p seed sequence. (I) Verification of Smad3 as a target gene of miR-145-5p utilizing the dual-luciferase reporter assay. Abbreviations: qRT-PCR, quantitative reverse transcription-polymerase chain reaction; VSMCs, vascular smooth muscle cells; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; DAPI, 4′,6-diamidino-2-phenylindole; Smad3, SMAD family member 3; OPN, Osteopontin; 22α, smooth muscle 22 alpha. ns: no significance. WT: wild type; MUT: mutant.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202500586","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FOXA2 loss results in an increase of endometriosis development and LIF reveals a therapeutic effect for endometriosis","authors":"Md Saidur Rahman,&nbsp;Tae Hoon Kim,&nbsp;Breton F. Barrier,&nbsp;Thomas E. Spencer,&nbsp;Andrew M. Kelleher,&nbsp;Jae-Wook Jeong","doi":"10.1096/fj.202403182R","DOIUrl":"https://doi.org/10.1096/fj.202403182R","url":null,"abstract":"<p>Endometriosis, characterized by the growth of uterine-like tissue outside the uterus, causes chronic pain and infertility. Current diagnostic and therapeutic strategies have notable limitations, including delayed diagnosis and adverse effects. The transcription factor forkhead box A2 (FOXA2), which is exclusively expressed in the uterine glandular epithelium, regulates key genes involved in endometrial proliferation, differentiation, fertility, and hormone response. While FOXA2 expression is reduced in the endometrial tissue of women with endometriosis, its pathophysiological role in the disease is not well understood. In this study, we report that endometriosis significantly reduced FOXA2 expression in the eutopic endometrium of mice with endometriosis compared to sham controls, accompanied by decreased expression of its downstream gene, CXCL15. To evaluate the effect of FOXA2 loss in endometriosis, we surgically induced endometriosis by transplanting control <i>Rosa26</i>^{<i>mTmG/+</i>} or <i>Pgr</i>^<i>cre/+</i><i>Foxa2</i>^<i>f/f</i><i>Rosa26</i>^{<i>mTmG/+</i>} (<i>Foxa2</i>^<i>d/d</i><i>Rosa26</i>^{<i>mTmG/+</i>}) endometrial tissue into the peritoneal cavity of mice. The number and weight of ectopic lesions were significantly increased in the mice with <i>Foxa2</i>^<i>d/d</i><i>Rosa26</i>^{<i>mTmG/+</i>} ectopic lesions compared to controls. Furthermore, progesterone receptor expression was significantly reduced in the endometrial epithelium from mice with <i>Foxa2</i>^<i>d/d</i><i>Rosa26</i>^{<i>mTmG/+</i>} ectopic lesions compared to mice with control ectopic lesions. Importantly, treatment with leukemia inhibitory factor (LIF), a cytokine regulated by FOXA2, significantly reduced ectopic lesion formation in <i>Foxa2</i>^<i>d/d</i><i>Rosa26</i>^{<i>mTmG/+</i>} endometriosis mice compared to vehicle-treated mice. This study demonstrates that FOXA2 loss results in an increase in endometriosis incidence and that treatment with LIF offers a novel promising therapeutic approach for endometriosis.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic aging and aging-related diseases","authors":"Qiao Li,&nbsp;Nanyin Xiao,&nbsp;Heng Zhang,&nbsp;Guangyu Liang,&nbsp;Yan Lin,&nbsp;Zonghao Qian,&nbsp;Xiao Yang,&nbsp;Jiankun Yang,&nbsp;Yanguang Fu,&nbsp;Cuntai Zhang,&nbsp;Anding Liu","doi":"10.1096/fj.202402479RRR","DOIUrl":"https://doi.org/10.1096/fj.202402479RRR","url":null,"abstract":"<p>Aging is a biological process along with systemic and multiple organ dysfunction. It is more and more recognized that aging is a systemic disease instead of a single-organ functional disorder. Systemic aging plays a profound role in multiple diseases including neurodegenerative diseases, cardiovascular diseases, and malignant diseases. Aged organs communicate with other organs and accelerate aging. Skeletal muscle, heart, bone marrow, skin, and liver communicate with each other through organ–organ crosstalk. The crosstalk can be mediated by metabolites including lipids, glucose, short-chain fatty acids (SCFA), inflammatory cytokines, and exosomes. Metabolic disorders including hyperglycemia, hyperinsulinemia, and hypercholesterolemia caused by chronic diseases accelerate hallmarks of aging. Systemic aging leads to the destruction of systemic hemostasis, causes the release of inflammatory cytokines, senescence-associated secretory phenotype (SASP), and the imbalance of microbiota composition. Released inflammatory factors further aggregate senescence, which promotes the aging of multiple solid organs. Targeting senescence or delaying aging is emerging as a critical health strategy for solving age-related diseases, especially in the old population. In the current review, we will delineate the mechanisms of organ crosstalk in systemic aging and age-related diseases to provide therapeutic targets for delaying aging.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202402479RRR","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insulin receptor responsiveness governs TGFβ-induced hepatic stellate cell activation: Insulin resistance instigates liver fibrosis","authors":"Wang-Hsin Lee,&nbsp;Evelyn A. Bates,&nbsp;Zachary A. Kipp,&nbsp;Sally N. Pauss,&nbsp;Genesee J. Martinez,&nbsp;Cheavar A. Blair,&nbsp;Terry D. Hinds Jr.","doi":"10.1096/fj.202402169R","DOIUrl":"https://doi.org/10.1096/fj.202402169R","url":null,"abstract":"<p>The insulin receptor (INSR) has been shown to be hyperactive in hepatic stellate cells (HSCs) in humans and rodents with liver fibrosis. To explore HSC cellular mechanisms that INSR regulates during pro-fibrotic stimulation, we used CRISPR-Cas9 technology. We knocked out a portion of the <i>INSR</i> gene in human LX2 HSC cells (<i>INSR</i>^e5-8 KO) that regulates insulin responsiveness but not the insulin-like growth factor (IGF) or transforming growth factor-β (TGFβ) signaling. The <i>INSR</i>^e5-8 KO HSCs had significantly higher cell growth, BrdU incorporation, and lower <i>TP53</i> expression that suppresses growth, and they also exhibited increased migration compared to the Scramble control. We treated the scramble control and <i>INSR</i>^e5-8 KO HSCs with insulin or TGFβ and profiled hundreds of kinase activities using the PamGene PamStation kinome technology. Our analysis showed that serine/threonine kinase (STK) activities were reduced, and most of the protein-tyrosine kinase (PTK) activities were increased in the <i>INSR</i>^e5-8 KO compared to the Scramble control HSCs. To study gene transcripts altered in activated Scramble control and <i>INSR</i>^e5-8 KO HSCs, we treated them with TGFβ for 24 h. We isolated RNA for sequencing and found that the <i>INSR</i>^e5-8 KO cells, compared to control HSCs, had altered transcriptional responsiveness to TGFβ stimulation, collagen-activated signaling, smooth muscle cell differentiation pathways, SMAD protein signaling, collagen metabolic process, integrin-mediated cell adhesion, and notch signaling. This study demonstrates that reduced INSR responsiveness enhances HSC growth and selectively mediates TGFβ-induced HSC activation. These findings provide new insights into the development of more effective treatments for liver fibrosis.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202402169R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel, rapidly progressive ataxia due to a spontaneous Myo5a mutation in mice impairs transport proteins and alters mitochondria","authors":"Alexander M. Telenson,&nbsp;Ryan R. Hsieh,&nbsp;Gabrielle J. Cowen,&nbsp;Eoin P. Sode,&nbsp;Jason M. Kwon,&nbsp;Andy H. Vo,&nbsp;Michele Hadhazy,&nbsp;Patrick G. Page,&nbsp;Nalini R. Rao,&nbsp;Lorenzo Pesce,&nbsp;Alexis R. Demonbreun,&nbsp;Megan J. Puckelwartz,&nbsp;Jeffrey N. Savas,&nbsp;Elizabeth M. McNally","doi":"10.1096/fj.202402274R","DOIUrl":"https://doi.org/10.1096/fj.202402274R","url":null,"abstract":"<p>Spontaneous mouse mutants have helped define genetic contributions to many phenotypes. Here we report a spontaneous Novel Ataxic Phenotype in mice. Ataxia findings were evident at post-natal day 11 in NAP mice and rapidly worsened, resulting in preweaning lethality. Using genome sequencing and genome-wide mapping, we identified a 3′ donor splice variant in exon 14 of <i>Myo5a</i>, encoding an actin-based motor protein. The variant in <i>Myo5a</i> (c.1752g&gt;a) excises exon 14 and ablates MYO5A protein expression, which is implicated in intracellular transport and Griscelli syndrome type I in humans. NAP mice displayed expansion of PAX6-positive cells in the external granule layer of the cerebellum, and mass spectrometry analysis of cerebellar extracts uncovered differentially abundant proteins involved in short-range organelle transport, and specifically proteins implicated with early endosomes. Using cerebellar lysates and primary neurons, we provide evidence for an interaction between MYO5A and ANKFY1, a known effector for the endosomal protein, RAB5A. We also found neurons from NAP mice had elongated mitochondria, linking MYO5A to mitochondrial homeostasis. This allele provides new insight into <i>Myo5a</i> function in developmental neuropathology.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143521873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting TUBG1 in RB1-negative tumors","authors":"Lisa Lindström,&nbsp;Jingkai Zhou,&nbsp;Bruno O. Villoutreix,&nbsp;Darina Malycheva,&nbsp;Magdalena Otrocka,&nbsp;Anna-Lena Gustavsson,&nbsp;Thomas Lundbäck,&nbsp;David Bliman,&nbsp;Muhammad Anwar Shameem,&nbsp;Megan Straw,&nbsp;Kristian Riesbeck,&nbsp;Roger Olsson,&nbsp;Maria Alvarado-Kristensson","doi":"10.1096/fj.202403180RR","DOIUrl":"https://doi.org/10.1096/fj.202403180RR","url":null,"abstract":"<p>The disruption of microtubule dynamics serves as a pivotal strategy for eliminating tumor cells, despite its accompanying toxicities affecting non-tumor cells. This study investigates the potential of selectively targeting γ-tubulin1 (TUBG1) as a therapeutic strategy in cancer treatment. By elucidating the TUBG1–E2F1–retinoblastoma protein (RB1) network, we introduce a novel compound, 4-(6-((3-Methoxyphenyl)amino)pyrimidin-4-yl)-N,N-dimethylbenzenamine, (L12). L12 treatment enhanced RB1 expression and selectively targeted cells with impaired RB1 signaling, while reduced E2F1 expression attenuated its cytotoxicity. Furthermore, L12-mediated cytotoxicity depends on an E2F1-mediated upregulation of procaspase 3 expression, highlighting the role of E2F1 in the apoptotic response. Unlike traditional tubulin-targeting agents, L12's specificity for tumor cells lies in its inhibitory effects on TUBG1, without affecting the second human isoform of TUBGs, TUBG2. Despite its interaction with specific kinases, the concentrations required for antitumor effects are 100-fold lower than those influencing kinase activities. Subsequent investigations underscore L12's reduced neuronal axonal toxicity compared to vincristine. Lastly, L12 demonstrates promising results in inhibiting tumor growth in xenografted small cell lung cancer models, demonstrating potential specificity toward tumor cells while minimizing adverse effects on healthy tissues. This research emphasizes the potential of TUBG1 inhibitors as a promising advancement in personalized chemotherapy approaches and their potential as a groundbreaking treatment for various cancers.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202403180RR","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative stress regulates the catalytic activity and mitochondrial localization of HK2 in trophoblast by regulating K346 lactylation","authors":"Zhirui Chen,&nbsp;Lingling Wan,&nbsp;Mengying Wu,&nbsp;Yun Zhao,&nbsp;Haixia Huang,&nbsp;Qiuyi He,&nbsp;Ying Wang,&nbsp;Qingqing Luo","doi":"10.1096/fj.202402430RR","DOIUrl":"https://doi.org/10.1096/fj.202402430RR","url":null,"abstract":"<p>Preeclampsia (PE) is one of the most dangerous complications of pregnancy. The pathogenic mechanisms of this condition are not yet clear. Lysine lactylation (Kla) is a novel post-translational modification (PTM) reported recently. It remains to be determined whether Kla plays a role in the development of PE. Here, western blotting revealed that the placental Kla profile of PE was different from that of normal pregnancies, and hydrogen peroxide (H₂O₂) weakened the Kla level of trophoblast cells. High-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) indicated that 333 Kla sites of 232 proteins were changed by Kla in BeWo cells (a trophoblast cell line) treated with H₂O₂, among which only HK2 showed a unique Kla site (K346) with down-regulated lactylation. Additionally, the inactive mutant HK2-K346 was associated with decreased hexokinase activity, lower affinity to voltage-dependent anion channel 1 (VDAC1), and impaired cell proliferation. These findings demonstrate that lactylation is involved in the pathogenesis of PE and that lactylation of HK2-K346 could serve as a new connection between oxidative stress, energy metabolism, and the development of PE.</p>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 5","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}