Cell death induction (extrinsic versus intrinsic apoptotic pathway) by intestinal ischemia–reperfusion injury in rats is time-depended

Ben-Shahar, Yoav; Abassi, Zaid; Pollak, Yulia; Koppelmann, Tal; Gorelik, Gregory; Sukhotnik, Igor

doi:10.1007/s00383-020-04817-7

Cited by 5 publications

(7 citation statements)

References 19 publications

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“…Apoptosis, a programmed cell death process, is involved in the pathogenesis of intestinal ischemia-reperfusion injury (30)(31)(32). The ratio of Bax/Bcl-2 is known to reflect the status of apoptosis, and its role in IRI has recently received widespread attention (8,33).…”

Section: Discussionmentioning

confidence: 99%

Prmt6-Foxo3a Attenuates Apoptosis by Upregulating Parkin Expression in Intestinal Ischemia-Reperfusion Injury

Wu,

Zhou,

et al. 2024

Shock

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Intestinal ischemia-reperfusion injury (IIRI) is a serious disease with high morbidity and mortality. This study aims to investigate the potential regulatory mechanisms involving protein arginine methyltransferase 6 (PRMT6), Forkhead box O3a (FoxO3a), and Parkin in IIRI and elucidate their roles in mediating cell apoptosis. The IIRI animal model was established and confirmed using Hematoxylin and Eosin (H&E) staining. Oxygen-glucose deprivation and reperfusion (OGD/R) cell model was established to mimic ischemic injury in vitro. Transient transfection was used to overexpress or knock down genes. Cell death or apoptosis was assessed by propidium iodide staining, TUNEL assay, and flow cytometry. The expression of proteins was detected by Western blot. The histopathology observed by HE staining suggested that the IIRI animal model was successfully established. Our findings revealed that IIRI resulted in increased Bax and decreased Bcl-2 levels. In vitro experiments showed that overexpression of Parkin decreased OGD/R injury and suppressed elevation of Bax/Bcl-2. PRMT6 regulated the methylation level of FoxO3a. Moreover, FoxO3a directly binds to Parkin, and FoxO3a overexpression reduced OGD/R-induced cell death and regulation of Parkin. Overexpression of PRMT6 can attenuate the downregulation of Parkin and elevation of Bax/Bcl-2 caused by OGD/R. Knockdown of PRMT6 promoted apoptosis in intestinal epithelial cells of OGD/R group, while PRMT6 overexpression exhibited the opposite effect. Notably, the levels of PRMT6, FoxO3a, and Parkin were decreased in IIRI mouse intestinal tissue. Knocking out PRMT6 causes a significant decrease in the lifespan of mice. Altogether, our results demonstrated that PRMT6 upregulated the expression of Parkin by regulating FoxO3a methylation level, attenuating the apoptosis induced by IIRI.

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Section: Discussionmentioning

confidence: 99%

Prmt6-Foxo3a Attenuates Apoptosis by Upregulating Parkin Expression in Intestinal Ischemia-Reperfusion Injury

Wu,

Zhou,

et al. 2024

Shock

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“…Bcl-2 is one of the key proteins that inhibit apoptosis. Bax, which belongs to the Bcl-2 family of proteins, can promote apoptosis ( Ben-Shahar et al, 2021 ). Combined analysis of the levels of Bcl-2 and Bax in the different groups showed that the treatment of transplanted HFMSCs reduced intestinal cell apoptosis ( Figure 7D ).…”

Section: Discussionmentioning

confidence: 99%

“…MSCs have also been suggested to alleviate oxidative stress by donating their mitochondria to damaged tissues (Ikeda et al, 1998). For a long time, oxidative stress injury was thought to mainly be due to the production of a large amount of reactive oxygen species (ROS) (Gonzalez et al, 2015), which can activate the immune response and destroy the function of the intestinal Frontiers in Cell and Developmental Biology frontiersin.org barrier (Ben-Shahar et al, 2021). ROS attack the membrane and lead to lipid peroxidation.…”

Section: Hfmscs Potential To Regulate Oxidative Stress and Improve In...mentioning

confidence: 99%

Transplanted hair follicle mesenchymal stem cells alleviated small intestinal ischemia–reperfusion injury via intrinsic and paracrine mechanisms in a rat model

Gao

Chen

Cang

et al. 2022

Front. Cell Dev. Biol.

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Background: Small intestinal ischemia-reperfusion (IR) injury is a common intestinal disease with high morbidity and mortality. Mesenchymal stem cells (MSCs) have been increasingly used in various intestinal diseases. This study aimed to evaluate the therapeutic effect of hair follicle MSCs (HFMSCs) on small intestinal IR injury.Methods: We divided Sprague–Dawley rats into three groups: the sham group, IR group and IR + HFMSCs group. A small intestinal IR injury rat model was established by clamping of the superior mesenteric artery (SMA) for 30 min and reperfusion for 2 h. HFMSCs were cultured in vitro and injected into the rats through the tail vein. Seven days after treatment, the intrinsic homing and differentiation characteristics of the HFMSCs were observed by immunofluorescence and immunohistochemical staining, and the paracrine mechanism of HFMSCs was assessed by Western blotting and enzyme-linked immunosorbent assay (ELISA).Results: A small intestinal IR injury model was successfully established. HFMSCs could home to damaged sites, express proliferating cell nuclear antigen (PCNA) and intestinal stem cell (ISC) markers, and promote small intestinal ISC marker expression. The expression levels of angiopoietin-1 (ANG1), vascular endothelial growth factor (VEGF) and insulin growth factor-1 (IGF1) in the IR + HFMSCs group were higher than those in the IR group. HFMSCs could prevent IR-induced apoptosis by increasing B-cell lymphoma-2 (Bcl-2) expression and decreasing Bcl-2 homologous antagonist/killer (Bax) expression. Oxidative stress level detection showed that the malondialdehyde (MDA) content was decreased, while the superoxide dismutase (SOD) content was increased in the IR + HFMSCs group compared to the IR group. An elevated diamine oxidase (DAO) level reflected the potential protective effect of HFMSCs on the intestinal mucosal barrier.Conclusion: HFMSCs are beneficial to alleviate small intestinal IR injury through intrinsic homing to the small intestine and by differentiating into ISCs, via a paracrine mechanism to promote angiogenesis, reduce apoptosis, regulate the oxidative stress response, and protect intestinal mucosal function potentially. Therefore, this study suggests that HFMSCs serve as a new option for the treatment of small intestinal IR injury.

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“…TNFR1, Fas) in the cell membrane and undergo a conformational change in the death-inducing signaling complex (DISC) to initiate cytotoxic signals by converting procaspases to caspases. Caspase-8, a crucial initiator caspase in the extrinsic pathway, directly cleaves and activates effector (executioner) caspases such as caspase-2, 3, 7 and 9, which induce apoptosis of damaged cells via proteolysis [ 120 – 122 ]. The intrinsic pathway, also called mitochondrial pathway, is activated under stressful conditions such as hypoxia during ischemia, and negatively impacts mitochondrial integrity, resulting in release of pro-apoptotic factors (e.g.…”

Section: Cell Death In Ischemia–reperfusion Injurymentioning

confidence: 99%

Cellular and molecular mechanisms of cell damage and cell death in ischemia–reperfusion injury in organ transplantation

Dugbartey

2024

Mol Biol Rep

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Ischemia–reperfusion injury (IRI) is a critical pathological condition in which cell death plays a major contributory role, and negatively impacts post-transplant outcomes. At the cellular level, hypoxia due to ischemia disturbs cellular metabolism and decreases cellular bioenergetics through dysfunction of mitochondrial electron transport chain, causing a switch from cellular respiration to anaerobic metabolism, and subsequent cascades of events that lead to increased intracellular concentrations of Na+, H+ and Ca2+ and consequently cellular edema. Restoration of blood supply after ischemia provides oxygen to the ischemic tissue in excess of its requirement, resulting in over-production of reactive oxygen species (ROS), which overwhelms the cells’ antioxidant defence system, and thereby causing oxidative damage in addition to activating pro-inflammatory pathways to cause cell death. Moderate ischemia and reperfusion may result in cell dysfunction, which may not lead to cell death due to activation of recovery systems to control ROS production and to ensure cell survival. However, prolonged and severe ischemia and reperfusion induce cell death by apoptosis, mitoptosis, necrosis, necroptosis, autophagy, mitophagy, mitochondrial permeability transition (MPT)-driven necrosis, ferroptosis, pyroptosis, cuproptosis and parthanoptosis. This review discusses cellular and molecular mechanisms of these various forms of cell death in the context of organ transplantation, and their inhibition, which holds clinical promise in the quest to prevent IRI and improve allograft quality and function for a long-term success of organ transplantation.

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Cell death induction (extrinsic versus intrinsic apoptotic pathway) by intestinal ischemia–reperfusion injury in rats is time-depended

Cited by 5 publications

References 19 publications

Prmt6-Foxo3a Attenuates Apoptosis by Upregulating Parkin Expression in Intestinal Ischemia-Reperfusion Injury

Prmt6-Foxo3a Attenuates Apoptosis by Upregulating Parkin Expression in Intestinal Ischemia-Reperfusion Injury

Transplanted hair follicle mesenchymal stem cells alleviated small intestinal ischemia–reperfusion injury via intrinsic and paracrine mechanisms in a rat model

Cellular and molecular mechanisms of cell damage and cell death in ischemia–reperfusion injury in organ transplantation

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