Endoplasmic Reticulum Stress Contributed to Dipyridamole-Induced Impaired Autophagic Flux and Glioma Apoptosis

Chang, Chieh-Ming J.; Wu, Chih-Cheng; Wang, Jiaan-Der; Liao, Su‐Lan; Chen, Wenying; Kuan, Yu‐Hsiang; Wang, Wenyi; Chen, Chun‐Jung

doi:10.3390/ijms23020579

Cited by 5 publications

(3 citation statements)

References 45 publications

(78 reference statements)

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“…The ER separates, stores and releases calcium in cells, and is involved in regulating gene transcription in the nucleus, energy metabolism in mitochondria and cytoplasmic signaling pathways ( 20 ). As a result of preventing phosphodiesterase-2, dipyridamole enhances ER stress-induced NoXA-guided apoptosis through an increase in intracellular cAMP levels ( 21 ). Blocking the interaction between IL-17A and ER stress attenuates LPS-induced lung injury ( 22 ).…”

Section: Discussionmentioning

confidence: 99%

Endoplasmic reticulum stress related IncRNA signature predicts the prognosis and immune response evaluation of uterine corpus endometrial carcinoma

Shen

Yang

2023

Front. Oncol.

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BackgroundEndoplasmic reticulum (ER) stress is closely related to the occurrence, development and treatment of tumors. Recent studies suggest ER stress as a therapeutic strategy of choice for cancer. However, ER stress-related long non-coding RNA (lncRNA) predictive value in endometrial carcinoma (UCEC) remains to be further evaluated. The purpose of this study was to establish relies on the signature of ER stress-related lncRNA forecast to predict the prognosis of patients with UCEC.MethodsWe downloaded the RNA expression profile dataset and matched clinical data from the Cancer Genome Atlas (TCGA) database, and applied univariate and multivariate Cox regression analysis to build predictive signature. Kaplan-meier method was used to evaluate overall survival (OS) and disease-free survival (DFS). Gene set enrichment analysis (GSEA) was used to study the functional characteristics. Single sample Gene set enrichment analysis (ssGSEA) was used to analyze the relationship between immune status and predicted signature. Correlations between the potential usefulness of treatment for UCEC patients and predictive signature were also analyzed.ResultsWe established a signature composed of eight ER stress-related lncRNAs (MIR34AHG, AC073842.2, PINK1AS, AC024909.2, MIR31HG, AC007422.2, AC061992.1, AC003102.1). The signature of ER stress-related lncRNA provided better diagnostic value compared with age and tumor grade, and the area under the receiver operating curve was 0.788. The overall and disease-free survival probability of patients in the high-risk group is lower than that in the low-risk group. GSEA indicated that the pathways were mainly enriched for cancer, immunity and reproduction related pathways. ss-GSEA shows that prediction signature and activation of dendritic cells, immature dendritic cells, T helper cells and immune status of the Treg are significantly related. High-risk groups may against PD - 1/L1 immunotherapy and JNK inhibitors VIII, Z.LLNle.CHO, DMOG and JNK. 9 l more sensitive.ConclusionThe ER stress signature can independently predict the prognosis of UCEC patients, and provide guidance for conventional chemotherapy and immunotherapy of UCEC patients.

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Section: Discussionmentioning

confidence: 99%

Endoplasmic reticulum stress related IncRNA signature predicts the prognosis and immune response evaluation of uterine corpus endometrial carcinoma

Shen

Yang

2023

Front. Oncol.

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“…In pregnancy, the blockade of autophagic flux takes part of disrupting homeostasis in trophoblasts 19 . In glioma, the autophagic flux is impaired 20 . The autophagic flux damaged in former diseases are related to ERS.…”

Section: Discussionmentioning

confidence: 99%

4-PBA inhibits endoplasmic reticulum stress to improve autophagic flux in the treatment of protamine/lipopolysaccharide-induced interstitial cystitis in rats

Jia,

Jingzhen,

Xinliang

et al. 2023

Sci Rep

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Interstitial cystitis (IC) has severe clinical symptoms with unclear mechanism. The continuous inflammatory response of the bladder is the basis of its pathogenesis. Endoplasmic reticulum stress (ERS) is involved in the regulation and development of various inflammatory diseases. And autophagy plays an important role in IC. In this study, we mainly focus on the therapeutic effect of endoplasmic reticulum stress and autophagy on protamine/lipopolysaccharide-induced interstitial cystitis. Female Sprague–Dawley rats were randomized into three experimental groups as follows: sham controls(N), IC alone, and IC+4-PBA.Rats in group IC received 10 mg/ml PS in the urinary bladder, followed by 2 mg/ml LPS instillation after 30 min, IC+4-PBA group SD rats received 4-PBA solution administered intragastrically once a day for 5 days. ERS biomarker (GRP78), autophagy-related proteins (LC3I/II, and Beclin1), autophagic flux biomarker (P62), inflammatory biomarkers (IL-6, TNF-a, NF-κB), apoptotic biomarkers (Caspase 3, Bax) were highest in the IC group compared to IC+4-PBA group and N group and the biomarkers expression in IC+4-PBA group were lower than in the IC group, anti-apoptotic biomarker (Bcl-2) was highest in the N group compared to the IC group and IC+4-PBA group and lower in the IC group than in the IC+4-PBA group, oxidative stress biomarkers (HO-1, NQO-1) were remarkably lower in the control group than in the IC and IC+4-PBA groups and notably lower in the IC group than in the IC+4-PBA group. The histological score and mast cell count demonstrated most severe in the IC group than those in the IC+4-PBA group. TUNEL assay examined the level of apoptosis in IC group was higher than in the IC+4-PBA group. The bladder micturition function was significantly improved with 4-PBA treatment. 4-PBA inhibits ERS to recover autophagic flux, and then to suppress the bladder oxidative stress, the inflammatory reaction and apoptosis, finally improve the bladder urinary function in Protamine/Lipopolysaccharide (PS/LPS) induced IC.

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“…In pregnancy, the blockade of autophagic ux takes part of disrupting homeostasis in trophoblasts 18 . In glioma, the autophagic ux is impaired 19 . The autophagic ux damaged in former diseases are related to ERS.…”

Section: Discussionmentioning

confidence: 99%

4-PBA inhibits endoplasmic reticulum stress to improve autophagic flux in the treatment of protamine/lipopolysaccharide-induced interstitial cystitis in rats

Zhu

Yang

et al. 2022

Preprint

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Interstitial cystitis (IC) has severe clinical symptoms with unclear mechanism. The continuous inflammatory response of the bladder is the basis of its pathogenesis. Endoplasmic reticulum stress (ERS) is involved in the regulation and development of various inflammatory diseases. And autophagy plays an important role in IC. In this study, we mainly focus on the therapeutic effect of endoplasmic reticulum stress and autophagy on protamine/lipopolysaccharide-induced interstitial cystitis. Female Sprague–Dawley rats were randomized into three experimental groupsas follows: sham controls(N), IC alone, and IC+4-PBA.Rats in group IC received 10 mg/ml PS in the urinary bladder, followed by 2 mg/ml LPS instillation after 30 minutes, IC +4-PBA group SD rats received 4-PBA solution administered intragastrically once a day for 5days.ERS biomarker (GRP78), autophagy-related proteins (LC3I/II, and Beclin1), autophagic flux biomarker (P62), inflammatory biomarkers (IL-6, TNF-a, NF-kB) , apoptotic biomarkers (Caspase 3, Bax), anti-apoptotic biomarkers (Bcl-2) and oxidative stress biomarkers (HO-1 , NQO-1)revealed significantly different results among the groups. The histological score and mast cell count demonstrated most severe in the IC group than those in the IC+USC group. TUNEL assay examined the level of apoptosis in IC group was higher than in the IC+USC group. The bladder micturition function was significantly improved with4-PBA treatment.4-PBA inhibits ERS to recover autophagic flux, and then to suppress the bladder oxidative stress, the inflammatory reaction and apoptosis, finally improve the bladder urinary function in PS/LPS induced IC.

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Endoplasmic Reticulum Stress Contributed to Dipyridamole-Induced Impaired Autophagic Flux and Glioma Apoptosis

Cited by 5 publications

References 45 publications

Endoplasmic reticulum stress related IncRNA signature predicts the prognosis and immune response evaluation of uterine corpus endometrial carcinoma

Endoplasmic reticulum stress related IncRNA signature predicts the prognosis and immune response evaluation of uterine corpus endometrial carcinoma

4-PBA inhibits endoplasmic reticulum stress to improve autophagic flux in the treatment of protamine/lipopolysaccharide-induced interstitial cystitis in rats

4-PBA inhibits endoplasmic reticulum stress to improve autophagic flux in the treatment of protamine/lipopolysaccharide-induced interstitial cystitis in rats

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