The Role of Endoplasmic Reticulum and Mitochondria in Maintaining Redox Status and Glycolytic Metabolism in Pluripotent Stem Cells

Babaei-Abraki, Shahnaz; Karamali, Fereshteh; Nasr-Esfahani, Mohammad Hossein

doi:10.1007/s12015-022-10338-8

Cited by 7 publications

(4 citation statements)

References 180 publications

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“…Generally, OXPHOS could induce lineage commitment and cell proliferation, while anaerobic oxidation tends to realize stem cell quiescence and maintenance [ 46 ]. The adjustment of mechanically-induced anaerobic oxidation is consistent with the maintenance of stem cell characteristics and stem cell quiescence [ 47 ]. However, as promising “seed cells” for periodontal tissue regeneration, plenty of studies have shown that the proliferation and differentiation of PDLSCs are of great significance for craniofacial tissue regeneration [ 8 , 9 ].…”

Section: Discussionmentioning

confidence: 91%

Mechanical force induces mitophagy-mediated anaerobic oxidation in periodontal ligament stem cells

Zhang

Cui

et al. 2023

Cell Mol Biol Lett

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Background The preference for glucose oxidative mode has crucial impacts on various physiological activities, including determining stem cell fate. External mechanical factors can play a decisive role in regulating critical metabolic enzymes and pathways of stem cells. Periodontal ligament stem cells (PDLSCs) are momentous effector cells that transform mechanical force into biological signals during the reconstruction of alveolar bone. However, mechanical stimuli-induced alteration of oxidative characteristics in PDLSCs and the underlying mechanisms have not been fully elucidated. Methods Herein, we examined the expression of LDH and COX4 by qRT-PCR, western blot, immunohistochemistry and immunofluorescence. We detected metabolites of lactic acid and reactive oxygen species for functional tests. We used tetramethylrhodamine methyl ester (TMRM) staining and a transmission electron microscope to clarify the mitochondrial status. After using western blot and immunofluorescence to clarify the change of DRP1, we further examined MFF, PINK1, and PARKIN by western blot. We used cyclosporin A (CsA) to confirm the regulation of mitophagy and ceased the stretching as a rescue experiment. Results Herein, we ascertained that mechanical force could increase the level of LDH and decrease the expression of COX4 in PDLSCs. Simultaneously, the yield of reactive oxygen species (ROS) in PDLSC reduced after stretching, while lactate acid augmented significantly. Furthermore, mitochondrial function in PDLSCs was negatively affected by impaired mitochondrial membrane potential (MMP) under mechanical force, and the augment of mitochondrial fission further induced PRKN-dependent mitophagy, which was confirmed by the rescue experiments via blocking mitophagy. As a reversible physiological stimulation, the anaerobic preference of PDLSCs altered by mechanical force could restore after the cessation of force stimulation. Conclusions Altogether, our study demonstrates that PDLSCs under mechanical force preferred anaerobic oxidation induced by the affected mitochondrial dynamics, especially mitophagy. Our findings support an association between mechanical stimulation and the oxidative profile of stem cells, which may shed light on the mechanical guidance of stem cell maintenance and commitment, and lay a molecular foundation for periodontal tissue regeneration. Graphical Abstract

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Section: Discussionmentioning

confidence: 91%

Mechanical force induces mitophagy-mediated anaerobic oxidation in periodontal ligament stem cells

Zhang

Cui

et al. 2023

Cell Mol Biol Lett

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“…Resolving how enhancement of OXPHOS activity by tumor spheroid formation influences cancer stem cell formation is a complex issue. Pluripotent stem cells (normal) and bulk tumor cells generally show glycolytic phenotype that is related both the generation of precursors for anabolic metabolism and the demands of rapidly growing cells [52][53][54][55]. Pluripotent stem cells switch to oxidative metabolism upon differentiation to multipotent, unipotent or terminal forms.…”

Section: Discussionmentioning

confidence: 99%

Spheroid architecture strongly induces miR-221/222 expression and promotes oxidative phosphorylation and survival of mobile tumor cells through a mechanism that includes restriction of miR-9 expression

Ward,

Hall,

Tree

et al. 2023

Preprint

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Tumor cell spheroids are three dimensional multicellular structures that form during the expansive growth of carcinoma cells. Spheroids support tumor metastasis as vehicles of dissemination, promoting growth and survival of bulk tumor and cancer stem cells within the mobile tumor cell population. Deciphering how spheroid architecture affects tumor cell phenotype will be essential for the development of therapeutics to inhibit transperitoneal metastasis and the development of peritoneal carcinomatosis by ovarian cancers. We investigated how spheroid formation directly affects OXPHOS activity and microRNA expression in a cultured ovarian carcinoma cell system. The rate of oxidative phosphorylation/respiration per cell in spheroids was nearly double that of the same cell type growing in suspension as single cells. Cells growing as spheroids showed greatly enhanced expression of miR-221/222, an oncomiR that targets multiple tumor suppressor genes, promotes invasion, as well as reduced expression of miR-9, which targets mitochondrial tRNA-modification enzymes and inhibits OXPHOS. Consistent with the greater efficiency of ATP generation afforded by OXPHOS phosphorylation, tumor cells growing as spheroids injected into the nutrient-poor environment of the murine peritoneum survived longer than the cells growing in suspension as loosely associated aggregates. The data suggest that in addition to the reported effects of spheroid formation on cancer cell growth and phenotype, including promotion of stem cell generation, spheroid architecture increases the OXPHOS activity of constituent tumor cells. During the mobile phase of metastasis, when ovarian tumor cells disperse through nutrient-poor environments such as the peritoneum, enhanced OXPHOS activity afforded by spheroid architecture would enhance survival and thereby contribute to metastatic potential.

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“…Glycolytic metabolism is the primary mode of self-renewal and maintenance in proliferating stem cells. To fulfil the increased energy (ATP) demand, stem cells switch from glycolytic to mitochondrial OXPHOS metabolism [77]. OXPHOS occurs within the mitochondria where the mitochondrial respiratory complexes and the ATP synthase create ATP.…”

Section: The Effects Of Rsv On Osteoblast-bone Forming Cellsmentioning

confidence: 99%

Revisiting Resveratrol as an Osteoprotective Agent: Molecular Evidence from In Vivo and In Vitro Studies

2023

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Resveratrol (RSV) (3,5,4′-trihydroxystilbene) is a stilbene found in abundance in berry fruits, peanuts, and some medicinal plants. It has a diverse range of pharmacological activities, underlining the significance of illness prevention and health promotion. The purpose of this review was to delve deeper into RSV’s bone-protective properties as well as its molecular mechanisms. Several in vivo studies have found the bone-protective effects of RSV in postmenopausal, senile, and disuse osteoporosis rat models. RSV has been shown to inhibit NF-κB and RANKL-mediated osteoclastogenesis, oxidative stress, and inflammation while increasing osteogenesis and boosting differentiation of mesenchymal stem cells to osteoblasts. Wnt/β-catenin, MAPKs/JNK/ERK, PI3K/AKT, FoxOs, microRNAs, and BMP2 are among the possible kinases and proteins involved in the underlying mechanisms. RSV has also been shown to be the most potent SIRT1 activator to cause stimulatory effects on osteoblasts and inhibitory effects on osteoclasts. RSV may, thus, represent a novel therapeutic strategy for increasing bone growth and reducing bone loss in the elderly and postmenopausal population.

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The Role of Endoplasmic Reticulum and Mitochondria in Maintaining Redox Status and Glycolytic Metabolism in Pluripotent Stem Cells

Cited by 7 publications

References 180 publications

Mechanical force induces mitophagy-mediated anaerobic oxidation in periodontal ligament stem cells

Mechanical force induces mitophagy-mediated anaerobic oxidation in periodontal ligament stem cells

Spheroid architecture strongly induces miR-221/222 expression and promotes oxidative phosphorylation and survival of mobile tumor cells through a mechanism that includes restriction of miR-9 expression

Revisiting Resveratrol as an Osteoprotective Agent: Molecular Evidence from In Vivo and In Vitro Studies

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