Identification of Cathepsin B as a Pharmacological Target for Ferroptosis after Spinal Cord Injury Via Combined Transcriptome Analysis

Ding, Yinghe; Sheng, Xiaolong; Shi, Chaoran; Yuan, Feifei; Liu, Yudong; Xie, Yong; Lü, Hongbin; Jiang, Liyuan; Hu, Jianzhong

doi:10.2139/ssrn.4165354

Cited by 3 publications

(2 citation statements)

References 72 publications

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“…The process results in the degradation of the antioxidant protein GPX4 and further ferroptosis [141]. In another study, inhibition of cathepsin B with CA-074-me reduced lipid oxidation, mitochondrial dysfunction, and ferroptotic cell death in spinal cord cells after spinal cord injury [151].…”

Section: Other Types Of Regulated Cell Deathmentioning

confidence: 98%

The Intricate Balance between Life and Death: ROS, Cathepsins, and Their Interplay in Cell Death and Autophagy

Voronina,

Frolova,

Kolesova

et al. 2024

IJMS

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Cellular survival hinges on a delicate balance between accumulating damages and repair mechanisms. In this intricate equilibrium, oxidants, currently considered physiological molecules, can compromise vital cellular components, ultimately triggering cell death. On the other hand, cells possess countermeasures, such as autophagy, which degrades and recycles damaged molecules and organelles, restoring homeostasis. Lysosomes and their enzymatic arsenal, including cathepsins, play critical roles in this balance, influencing the cell’s fate toward either apoptosis and other mechanisms of regulated cell death or autophagy. However, the interplay between reactive oxygen species (ROS) and cathepsins in these life-or-death pathways transcends a simple cause-and-effect relationship. These elements directly and indirectly influence each other’s activities, creating a complex web of interactions. This review delves into the inner workings of regulated cell death and autophagy, highlighting the pivotal role of ROS and cathepsins in these pathways and their intricate interplay.

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Section: Other Types Of Regulated Cell Deathmentioning

confidence: 98%

The Intricate Balance between Life and Death: ROS, Cathepsins, and Their Interplay in Cell Death and Autophagy

Voronina,

Frolova,

Kolesova

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…Currently, CtsB is the subject of numerous studies aimed at developing inhibitors to mitigate its activity in various conditions. The efficacy of CtsB inhibition has been tested in ameliorating a spinal cord injury by inhibiting macrophage ferroptosis [15] and treating cancer through the development of small molecules, such as the Nostoc-species-derived oxadiazine Nocuolin A [16], or biologics based on peptides [17,18]. The critical roles and regulatory pathways mediated by CtsB in various forms of regulated cell death, including pyroptosis, ferroptosis, necroptosis and apoptosis [19], make this enzyme highly attractive for developing new strategies based on inhibitory approaches.…”

Section: Introductionmentioning

confidence: 99%

Smart Delivery Systems Responsive to Cathepsin B Activity for Cancer Treatment

et al. 2023

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Cathepsin B is a lysosomal cysteine protease, contributing to vital cellular homeostatic processes including protein turnover, macroautophagy of damaged organelles, antigen presentation, and in the extracellular space, it takes part in tissue remodeling, prohormone processing, and activation. However, aberrant overexpression of cathepsin B and its enzymatic activity is associated with different pathological conditions, including cancer. Cathepsin B overexpression in tumor tissues makes this enzyme an important target for smart delivery systems, responsive to the activity of this enzyme. The generation of technologies which therapeutic effect is activated as a result of cathepsin B cleavage provides an opportunity for tumor-targeted therapy and controlled drug release. In this review, we summarized different technologies designed to improve current cancer treatments responsive to the activity of this enzyme that were shown to play a key role in disease progression and response to the treatment.

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Prolyl 4-hydroxylase subunit beta (P4HB) could serve as a prognostic and radiosensitivity biomarker for prostate cancer patients

et al. 2023

Eur J Med Res

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Background Prolyl 4-hydroxylase subunit beta (P4HB) has been reported as a suppressor in ferroptosis. However, no known empirical research has focused on exploring relationships between P4HB and prostate cancer (PCa). In this research, we initially examine the function of P4HB in PCa by thorough analysis of numerous databases and proliferation experiment. Methods We analyzed the correlations of P4HB expression with prognosis, clinical features, mutation genes, tumor heterogeneity, stemness, tumor immune microenvironment and PCa cells using multiple databases and in vitro experiment with R 3.6.3 software and its suitable packages. Results P4HB was significantly upregulated in tumor tissues compared to normal tissues and was closely related to biochemical recurrence-free survival. In terms of clinical correlations, we found that higher P4HB expression was significantly related to older age, higher Gleason score, advanced T stage and residual tumor. Surprisingly, P4HB had highly diagnostic accuracy of radiotherapy resistance (AUC 0.938). TGF beta signaling pathway and dorso ventral axis formation were upregulated in the group of low-expression P4HB. For tumor stemness, P4HB expression was positively related to EREG.EXPss and RNAss, but was negatively associated with ENHss and DNAss with statistical significance. For tumor heterogeneity, P4HB expression was positively related to MATH, but was negatively associated with tumor ploidy and microsatellite instability. For the overall assessment of TME, we observed that P4HB expression was negatively associated with all parameters, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, dendritic cells, stromal score, immune score and ESTIMATE score. Spearman analysis showed that P4HB expression was negatively related to TIDE score with statistical significance. In vitro experiment, RT-qPCR and western blot showed that three siRNAs of P4HB were effective on the knockdown of P4HB expression. Furthermore, we observed that the downregulation of P4HB had significant influence on the cell proliferation of six PCa cell lines, including LNCap, C4-2, C4-2B, PC3, DU145 and 22RV1 cells. Conclusions In this study, we found that P4HB might serve as a prognostic biomarker and predict radiotherapy resistance for PCa patients. Downregulation of P4HB expression could inhibit the cell proliferation of PCa cells.

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Identification of Cathepsin B as a Pharmacological Target for Ferroptosis after Spinal Cord Injury Via Combined Transcriptome Analysis

Cited by 3 publications

References 72 publications

The Intricate Balance between Life and Death: ROS, Cathepsins, and Their Interplay in Cell Death and Autophagy

The Intricate Balance between Life and Death: ROS, Cathepsins, and Their Interplay in Cell Death and Autophagy

Smart Delivery Systems Responsive to Cathepsin B Activity for Cancer Treatment

Prolyl 4-hydroxylase subunit beta (P4HB) could serve as a prognostic and radiosensitivity biomarker for prostate cancer patients

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