Lactylation stabilizes DCBLD1 activating the pentose phosphate pathway to promote cervical cancer progression

Journal of Experimental & Clinical Cancer Research, Год журнала: 2024, Номер 43(1)

Опубликована: Янв. 31, 2024

Abstract Background Discoidin, CUB, and LCCL domain-containing type I (DCBLD1) is identified as an oncogene involved in multiple regulation of tumor progression, but specific mechanisms remain unclear cervical cancer. Lactate-mediated lactylation modulates protein function. Whether DCBLD1 can be modified by the function are unknown. Therefore, this study aims to investigate identify its sites. Herein, we elucidated mechanism which modification stabilizes protein. Furthermore, investigated overexpression activating pentose phosphate pathway (PPP) promote progression Methods expression was examined human cancer cells adjacent non-tumorous tissues using quantitative reverse transcription-polymerase chain reaction, western blotting, immunohistochemistry. In vitro vivo studies were conducted impact on Untargeted liquid chromatography-tandem mass spectrometry (LC–MS/MS) metabolomics used characterize DCBLD1-induced metabolite alterations. Western blot, immunofuorescence transmission electron microscopy performed detect degradation G6PD autophagy. Chromatin immunoprecipitation, dual luciferase reporter assay for detecting lactate increases transcription. LC–MS/MS employed verify sites within Results We found that increased expression, PPP facilitate proliferation metastasis cells. primarily stimulated upregulating glucose-6-phosphate dehydrogenase (G6PD) enzyme activity. The enrichment HIF-1α promoter region, enhancing mRNA expression. Additionally, lactate-induced stabilized a substrate, with predominant site at K172. inhibited autophagic degradation, progression. vivo, 6-An mediated inhibition activity, inhibiting proliferation. Conclusions Our findings revealed novel post-translational DCBDL1, emphasizing significance lactylation-driven DCBDL1-mediated promoting Graphical Schematic illustration G6PD-mediated reprogramming metabolism

Язык: Английский

---

Glycolysis, the sweet appetite of the tumor microenvironment

Cancer Letters, Год журнала: 2024, Номер 600, С. 217156 - 217156

Опубликована: Авг. 8, 2024

Cancer cells display an altered metabolic phenotype, characterised by increased glycolysis and lactate production, even in the presence of sufficient oxygen - a phenomenon known as Warburg effect. This reprogramming is crucial adaptation that enables cancer to meet their elevated energy biosynthetic demands. Importantly, tumor microenvironment plays pivotal role shaping sustaining this shift cells. review explores intricate relationship between effect, highlighting how communication within niche regulates cell metabolism impacts progression therapeutic resistance. We discuss potential targeting effect promising strategy, with aim disrupting advantage enhancing our understanding complex interplay microenvironment.

Язык: Английский

---

Senotherapeutics to Counteract Senescent Cells Are Prominent Topics in the Context of Anti-Ageing Strategies

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(3), С. 1792 - 1792

Опубликована: Фев. 1, 2024

Cellular senescence is implicated in ageing and associated with a broad spectrum of age-related diseases. Importantly, cell can initiate the program irrespective organism’s age. Various stress signals, including those defined as hallmarks alterations leading to cancer development, oncogene activation, or loss cancer-suppressive functions, trigger cellular senescence. The primary outcome these activation nuclear factor (NF)-κB, thereby inducing senescence-associated secretory phenotype (SASP). Proinflammatory cytokines chemokines, components this phenotype, contribute chronic systemic sterile inflammation, commonly referred inflamm-ageing. This inflammation linked diseases (ARDs), frailty, increased mortality older individuals. Additionally, senescent cells (SCs) accumulate multiple tissues age are believed underlie organism functional decline, demonstrated by models. An escalating effort has been dedicated identify senotherapeutics that selectively target SCs apoptosis; drugs termed senolytics. Concurrently, small molecules suppress phenotypes without causing death known senomorphics. Both natural synthetic senotherapeutics, along immunotherapies employing immune cell-mediated clearance SCs, currently represent most promising strategies combat ARDs. Indeed, it fascinating observe information regarding reaction indicates regulation specific lymphocyte subsets, elevated oldest centenarians, plays role attaining extreme longevity. Regardless, application methods already utilized treatment, such CAR monoclonal antibodies, broadens potential approaches be utilized.

Язык: Английский

---

Metabolic remodeling in cancer and senescence and its therapeutic implications

Trends in Endocrinology and Metabolism, Год журнала: 2024, Номер 35(8), С. 732 - 744

Опубликована: Март 6, 2024

Язык: Английский

---

Association between fatigue, peripheral serotonin, and L-carnitine in hypothyroidism and in chronic fatigue syndrome

Frontiers in Endocrinology, Год журнала: 2024, Номер 15

Опубликована: Март 5, 2024

Background Fatigue of unknown origin is a hallmark symptom in chronic fatigue syndrome (CFS) and also found 20% hypothyroidism patients despite appropriate levothyroxine treatment. Here, we suggest that these disorders, peripheral serotonin levels are low, elevating them to normal range with L-carnitine accompanied reduced fatigue. Methods We conducted retrospective analysis follow-up clinical data (CFS N=12; N=40) where serum were compared before vs. after 7 weeks oral supplementation. Results After L-carnitine, increased (8-fold CFS, Sig. = 0.002, 6-fold hypothyroidism, < 0.001) whereas decreased (2-fold both CFS 0.002 for 0.001 hypothyroidism). There was negative correlation between level (for rho -0.49 -0.67 L-carnitine; -0.24 -0.83 L-carnitine). Conclusions These findings new link low serotonin,

Язык: Английский

---

Metabolic reprogramming and synergistic cytotoxicity of genistein and chemotherapy in human breast cancer cells

Life Sciences, Год журнала: 2025, Номер unknown, С. 123562 - 123562

Опубликована: Март 1, 2025

Язык: Английский

---

Obesity-induced Neuronal Senescence: Unraveling the Pathophysiological Links

Ageing Research Reviews, Год журнала: 2024, Номер unknown, С. 102533 - 102533

Опубликована: Окт. 1, 2024

Язык: Английский

---

METTL3 and FTO Regulate Heat Stress Response in Hu Sheep Through Lipid Metabolism via m6A Modification

Animals, Год журнала: 2025, Номер 15(2), С. 193 - 193

Опубликована: Янв. 13, 2025

In an established hepatocyte lipid deposition heat stress model, the expression levels of METTL3 and FTO were significantly upregulated (p < 0.05), indicating that play important roles in process hepatocytes. Transcriptome metabolome analyses showed had significant effects on linoleic acid, linolenic glycerophospholipid, arachidonic acid metabolic pathways After knockdown, m6A methylation level decreased, but difference was not > FABP4 Accα increased, HSP60, HSP70, HSP110 decreased significantly. overexpression, increased FABP4, ATGL, Accα, HSP90, significantly, overexpression reduced shock genes by inhibiting lipid-deposition-related gene m6A-dependent manner. The after while HSP110, reduced. Following ATGL increased. This indicates promoted manner to reduce genes. sequencing screened a large number differential metabolites, KEGG enrichment analysis mainly regulated affecting TNF, cAMP, MAPK, lipolysis, synthesis model preadipocytes, regulation similar

Язык: Английский

---

Hexaraphane Affects the Activation of Hepatic PPARα Signaling: Impact on Plasma Triglyceride Levels and Hepatic Senescence with Aging

Nutrients, Год журнала: 2025, Номер 17(11), С. 1768 - 1768

Опубликована: Май 23, 2025

Background/Objectives: Hexaraphane, also known as 6-methylsulfinylhexyl isothiocyanate, derived from wasabi (Eutrema japonicum), increases heme oxygenase-1 (HO-1) and aldehyde dehydrogenase 2 (ALDH2) mRNA expression by activating nuclear factor erythroid 2-related (Nrf2) in both HepG2 cells the mouse liver. Given presence of a peroxisome proliferator-activated receptor (PPAR) response element (PPRE) HO-1 ALDH2 promoters, present study aimed to determine effects hexaraphane on PPARα-associated genes, age-related weight gain, plasma triglyceride levels, hepatic senescence. Methods: were treated with evaluate PPARα target gene PPRE transcriptional activity. Male C57BL/6J young control, aged mice administered for 16 weeks assessed food water intake, body tissue weights, parameters, PPARα-related expression. Results: Hexaraphane increased levels cells, which was inhibited GW6471, antagonist. It elevated activity carnitine palmitoyltransferase 1A (CPT1A) indicating activation. In mice, intake reduced gain decreasing adipose weight. Increased CPT1A tendency toward acyl-CoA oxidase 1 (ACOX1) liver associated gain. Sirt1 lower levels. suggest positive feedback loop between Sirt1. The p21 mRNA, senescence marker regulated Sirt1, upregulated but suppressed intake. Conclusions: may prevent PPARα, potentially contributing longevity.

Язык: Английский

---

Influence of a Zombie-like State of the Liver on Drugs and Its Medico-Legal Implications: A Scoping Review

Pharmaceuticals, Год журнала: 2025, Номер 18(6), С. 787 - 787

Опубликована: Май 24, 2025

When cells remain permanently trapped in a particular cell cycle stage, they are senescence. This also occurs the liver. Such often referred to as “zombie cells”, and an entire organ filled with these cells” is said be “zombie-like” state, characterized by lack of function. The senescence-associated secretory phenotype (SASP) encompasses substances release, which can significantly affect nearby tissues. While cellular senescence SASP related concepts, distinct. scoping review aims clarify role hepatocyte administration pharmaceuticals, well their relevance medico-legal practice, disability claims, insurance coverage. In this context, effects pharmaceuticals on senescent hepatocytes discussed, particularly regarding implications likely abused. conclusion, may relevant clinical or work because it sheds new light interpreting findings expert witness statements.

Язык: Английский

---