Characterization of Endoplasmic Reticulum (ER) in Human Pluripotent Stem Cells Revealed Increased Susceptibility to Cell Death upon ER Stress

Ha, Tae Won; Jeong, Ji Hun; Shin, HyeonSeok; Kim, Hyun Kyu; Im, Jeong Suk; Song, Byung Hoo; Hanna, Jacob; Oh, Jae Sang; Woo, Dong Hun; Han, Jaeseok; Lee, Man Ryul

doi:10.3390/cells9051078

Cited by 13 publications

(7 citation statements)

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“…In the present study, we could not discover the reasons for the different reaction of ER stress in the endometrial epithelial and stromal cells under hyperthermia conditions. However, since the structure of ER is involved in the intensity of ER stress (Ha et al, 2020), the different reaction of ER stress against hyperthermia in the two types of endometrial cells might be caused by the different of their ER structure and endometrial stromal cells might be more sensitive to hyperthermia than endometrial epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

Hyperthermia alters interleukin‐6 production in response to lipopolysaccharide via endoplasmic reticulum stress in bovine endometrial cells

Sakai

Inoue

Tanaka

et al. 2021

Journal Cellular Physiology

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In the postpartum period, cows experience the uterine bacterial infection and develop the endometritis. To eliminate bacteria and recover from endometritis, endometrial epithelial and stromal cells secrete the cytokine and chemokine, such as interleukin 6 (IL-6), IL-8, and monocyte chemotactic protein 1 (MCP1), to recruit immune cells. Moreover, the symptom of endometritis is prolonged in summer and we have recently indicated that hyperthermia suppresses and enhances the IL-6 production in response to lipopolysaccharide (LPS) challenge in endometrial epithelial and stromal cells, respectively. However, the mechanisms for the opposite reaction of IL-6 secretion in response to LPS challenge in both types of endometrial cells under hyperthermia conditions were still unclear. To reveal these mechanisms, both types of endometrial cells were cultured with LPS under the control (38.5°C) or hyperthermia (40.5°C) conditions and comprehensively analyzed differential gene expressions of them by RNA-seq. In addition, based on these results, we examined the effect of endoplasmic reticulum (ER) stress on the IL-6 production in both types of endometrial cells cultured with LPS under hyperthermia conditions. In comprehensive analysis, hyperthermia induced the ER stress in the endometrial stromal cells but not in the endometrial epithelial cells. Actually, we confirmed that hyperthermia increased the gene expression of BiP, ATF4, and sXBP1 and protein expression of BiP and phosphorylated inositol requiring 1, ER stress marker, in the endometrial stromal cells but not in the endometrial epithelial cells. Moreover, in the endometrial stromal cells exposed to LPS, activation and inhibition of ER stress enhanced the IL-6 production under control conditions and suppressed it under hyperthermia conditions, respectively. In this study, we could uncover the one of causes for the disruption of IL-6 production in response to LPS challenge in the endometrial cells under hyperthermia conditions. This finding might be a clue for the improvement of the symptom of endometritis in cows during summer.

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Section: Discussionmentioning

confidence: 99%

Hyperthermia alters interleukin‐6 production in response to lipopolysaccharide via endoplasmic reticulum stress in bovine endometrial cells

Sakai

Inoue

Tanaka

et al. 2021

Journal Cellular Physiology

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“…To further validate the presence of ER stress and UPR response in MRTs, we performed transmission electron microscopy (TEM) on normal kidney and MRT organoid samples. Although kidney organoid cells showed a healthy-structured ER (Figures 4E, top left, and S3L), MRT cells displayed more, but thinner and fragmented, ER, accompanied by an increased presence of lipid droplets and helical ER filaments; altogether, these are signs of ER stress and UPR activation (Bernales et al, 2006;Carter et al, 2021;Ha et al, 2020;Li et al, 2008;Lu et al, 2020) and S3L). These MRT-specific phenotypes were also accompanied by the first signs of apoptosis and necrosis (Figure S3L).…”

Section: Low-dose Mln4924 Treatment Induces Apoptosis In Mrtmentioning

confidence: 93%

Organoid-based drug screening reveals neddylation as therapeutic target for malignant rhabdoid tumors

et al. 2021

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“…The membranes were washed thrice for 15 min with TBS-T at room temperature and incubated for < 1.5 h at room temperature with secondary antibodies. Chemiluminescence detection was performed using the Pico EPD Western Blot Detection Kit (Elpis Biotech) [27].…”

Section: Western Blotting Western Blottingmentioning

confidence: 99%

Albumin-binding photosensitizer capable of targeting glioma via the SPARC pathway

Lee

et al. 2023

Preprint

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Background Malignant glioma is among the most lethal and frequently occurring brain tumors, and the average survival period is 15 months. Existing chemotherapy has low tolerance and low blood-brain barrier (BBB) permeability; therefore, the required drug dose cannot be accurately delivered to the tumor site, resulting in an insufficient drug effect. Methods Herein, we demonstrate a precision photodynamic tumor therapy using a photosensitizer (ZnPcS) capable of binding to albumin in situ, which can increase the permeability of the BBB and accurately target glioma. Albumin-binding ZnPcS was designed to pass through the BBB and bind to secreted protein acidic and rich in cysteine (SPARC), which is abundant in the glioma plasma membrane. Results When the upper part of a mouse brain was irradiated using a laser (0.2 W cm− 2) after transplantation of glioma and injection of ZnPcS, tumor growth was inhibited by approximately 83.6%, and the 50% survival rate of the treatment group increased by 14 days compared to the control group. In glioma with knockout SPARC, the amount of ZnPcS entering the glioma was reduced by 63.1%, indicating that it can target glioma through the SPARC pathway. Conclusions This study showed that using albumin-binding photosensitizers is promising for the treatment of malignant gliomas.

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Characterization of Endoplasmic Reticulum (ER) in Human Pluripotent Stem Cells Revealed Increased Susceptibility to Cell Death upon ER Stress

Cited by 13 publications

References 50 publications

Hyperthermia alters interleukin‐6 production in response to lipopolysaccharide via endoplasmic reticulum stress in bovine endometrial cells

Hyperthermia alters interleukin‐6 production in response to lipopolysaccharide via endoplasmic reticulum stress in bovine endometrial cells

Organoid-based drug screening reveals neddylation as therapeutic target for malignant rhabdoid tumors

Albumin-binding photosensitizer capable of targeting glioma via the SPARC pathway

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