Uncoupling Protein Overexpression in Metabolic Disease and the Risk of Uncontrolled Cell Proliferation and Tumorigenesis

Ruiz-Ramírez, Angélica; López-Acosta, Ocarol; Barrios-Maya, Miguel Angel; El-Hafidi, Mohammed

doi:10.2174/1566524018666180308110822

Cited by 7 publications

(3 citation statements)

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“…As OXPHOS processes generate large quantities of protons that induce important pH alterations, under normal conditions, cardiolipin traps protons within the mitochondrial membrane, minimizing the pH changes (35). The protective mechanism is overridden in tumor cells, leading to mitochondrial activity dysfunction (36). Indeed, as suggested by Kiebiesh et al in tumor cells, lipid and electron transport dysfunctionalities of the mitochondria are hallmarks of metabolic deregulations (37).…”

Section: Tumor Cell Metabolism Is Sustained By Mitochondrial Biochemimentioning

confidence: 99%

Inflammation and Metabolism in Cancer Cell—Mitochondria Key Player

et al. 2019

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Cancer metabolism is an essential aspect of tumorigenesis, as cancer cells have increased energy requirements in comparison to normal cells. Thus, an enhanced metabolism is needed in order to accommodate tumor cells' accelerated biological functions, including increased proliferation, vigorous migration during metastasis, and adaptation to different tissues from the primary invasion site. In this context, the assessment of tumor cell metabolic pathways generates crucial data pertaining to the mechanisms through which tumor cells survive and grow in a milieu of host defense mechanisms. Indeed, various studies have demonstrated that the metabolic signature of tumors is heterogeneous. Furthermore, these metabolic changes induce the exacerbated production of several molecules, which result in alterations that aid an inflammatory milieu. The therapeutic armentarium for oncology should thus include metabolic and inflammation regulators. Our expanding knowledge of the metabolic behavior of tumor cells, whether from solid tumors or hematologic malignancies, may provide the basis for the development of tailor-made cancer therapies.

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Section: Tumor Cell Metabolism Is Sustained By Mitochondrial Biochemimentioning

confidence: 99%

Inflammation and Metabolism in Cancer Cell—Mitochondria Key Player

et al. 2019

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“…It has been shown that overexpression of UCP2 protected VSMCs against hypertension and other cardiovascular diseases through upregulation of mitochondrial uncoupling [ 28 , 29 ]. Mitochondrial uncoupling plays an important role in regulation of cell function, which decreases mitochondrial ROS generation and metabolic stress [ 30 ]. Here, we found that Ang II treatment increased mitochondrial membrane potential and mitochondrial uncoupling in VSMCs, which was associated with the downregulation of Bcl-xL.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of miR-140-5p uncouples mitochondria by targeting Bcl-xL in vascular smooth muscle cells in angiotensin II-induced hypertension

Tuo

Zhang

et al. 2022

Bioengineered

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Angiotensin II–induced vascular smooth muscle cell (VSMC) remodeling and dysfunction is a major contributor to the development of hypertension. In spite of the low content of mitochondria and their low contribution to bioenergetics in VSMCs, recent studies have suggested that mitochondria play an important role in the regulation of VSMC function. However, the role of mitochondria in angiotensin II–induced VSMC dysfunction remains unknown. Here, we found that angiotensin II decreased the expression of Bcl-2-like protein 1 (Bcl-xL), a newly identified protein in inhibition of uncoupled proton flux in mitochondria through interaction with the β-subunit of ATP synthase, and uncoupled mitochondria in VSMCs both in vivo and in vitro. Overexpression of Bcl-xL restored the mitochondrial and VSMC function in response to angiotensin II treatment in vitro, suggesting that angiotensin II uncouples mitochondria through downregulation of Bcl-xL. Mechanistically, angiotensin II increased the expression of miR-140-5p, which targeted and downregulated Bcl-xL in VSMCs. Inhibition of miR-140-5p using antagomir-140-5p in vivo attenuated mitochondrial uncoupling and hypertension in angiotensin II-treated mice. These results suggested that upregulation of miR-140-5p uncouples mitochondria by targeting Bcl-xL in VSMCs in angiotensin II–induced hypertension, and miR-140-5p and Bcl-xL are potential targets for treatment of vascular dysfunction.

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“…Significant increase in superoxide level following burn injury and oxidative damage to tissues are implicated in inflammation, systemic inflammatory response syndrome, severe injury, infection, sepsis, and multiple organ failure. Recent studies have demonstrated that superoxide induces uncoupling process in mitochondria, and that uncoupling is correlated with UCP-1 expression in different tissues, but not in those not expressing UCPs, such as liver [18][19][20]. The expression of UCP-1 in BAT occurs in mitochondria and is a nucleotide-sensitive process [21].…”

Section: Discussionmentioning

confidence: 99%

Effect of celecoxib in treatment of burn-induced hypermetabolism

Zhuang

Chai²,

Liu³

et al. 2020

Bioscience Reports

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Background: Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step of prostanoid biosynthesis. Under pathologic conditions, COX-2 activity can produce reactive oxygen species and toxic prostaglandin metabolites that exacerbate injury and metabolic disturbance. The present study was performed to investigate the effect of Celecoxib (the inhibitor of COX-2) treatment on lipolysis in burn mice. Methods: One hundred male BALB/c mice were randomly divided into sham group, burn group, celecoxib group, and burn with celecoxib group (25 mice in each group). Thirty percent total body surface area (TBSA) full-thickness injury was made for mice to mimic burn injuries. Volume of oxygen uptake (VO2), volume of carbon dioxide output (VCO2), respiratory exchange ratio (RER), energy expenditure (EE), COX-2 and uncoupled protein-1 (UCP-1) expression in brown adipose tissue (BAT) were measured for different groups. Results: Adipose tissue (AT) activation was associated with the augmentation of mitochondria biogenesis, and UCP-1 expression in isolated iBAT mitochondria. In addition, VO2, VCO2, EE, COX-2, and UCP-1 expression were significantly higher in burn group than in burn with celecoxib group (P<0.05). Conclusion: BAT plays important roles in burn injury-induced hypermetabolism through its morphological changes and elevating the expression of UCP-1. Celecoxib could improve lipolysis after burn injury.

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Uncoupling Protein Overexpression in Metabolic Disease and the Risk of Uncontrolled Cell Proliferation and Tumorigenesis

Cited by 7 publications

References 0 publications

Inflammation and Metabolism in Cancer Cell—Mitochondria Key Player

Inflammation and Metabolism in Cancer Cell—Mitochondria Key Player

Upregulation of miR-140-5p uncouples mitochondria by targeting Bcl-xL in vascular smooth muscle cells in angiotensin II-induced hypertension

Effect of celecoxib in treatment of burn-induced hypermetabolism

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