MnTE-2-PyP protects fibroblast mitochondria from hyperglycemia and radiation exposure

Chatterjee, Arpita; Sakallioglu, Isin T.; Murthy, Divya; Kosmacek, Elizabeth A.; Singh, Pankaj K.; McDonald, J. Tyson; Powers, Robert; Oberley‐Deegan, Rebecca E.

doi:10.1016/j.redox.2022.102301

Cited by 7 publications

(4 citation statements)

References 77 publications

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“…Consistent with before [ 8 ],FoxO3a activation induced by glucose deprivation decreased total levels of OXPHOS complex in erastin treated cells. We measured total levels of PGC1α, an important regulator of mitochondrial biogenesis [ 25 ]and mitochondria marker TOM20 in our studies. We found glucose deprivation decreased the total expression of PGC1α and TOM20, indicating energy stress decreased mitochondrial biogenesis in erastin-treated conditions.…”

Section: Discussionmentioning

confidence: 99%

Energy stress modulation of AMPK/FoxO3 signaling inhibits mitochondria-associated ferroptosis

et al. 2023

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Section: Discussionmentioning

confidence: 99%

Energy stress modulation of AMPK/FoxO3 signaling inhibits mitochondria-associated ferroptosis

et al. 2023

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“…Cancer cells must manage oxidative stress by maintaining reactive oxygen species (ROS) levels within a narrow range 76 . Disruption of cancer cell ROS homeostasis can occur downstream of many different metabolic perturbations (such as hyperglycaemia) 77 or genotoxic perturbations (such as gemcitabine) 78 or via changes in the microenvironment (such as acidosis) 79 , commonly by depletion of the cellular antioxidants NADPH and reduced glutathione (GSH). Interestingly, the pyrimidine nucleosides uridine 80 , 81 and deoxyuridine 78 have emerged as powerful relievers of oxidative stress.…”

Section: Effects Of Inhibiting (D)ntp Synthesis On Growth and Prolife...mentioning

confidence: 99%

Nucleotide metabolism: a pan-cancer metabolic dependency

2023

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Metabolic alterations are a key hallmark of cancer cells, and the augmented synthesis and use of nucleotide triphosphates is a critical and universal metabolic dependency of cancer cells across different cancer types and genetic backgrounds. Many of the aggressive behaviours of cancer cells, including uncontrolled proliferation, chemotherapy resistance, immune evasion and metastasis, rely heavily on augmented nucleotide metabolism. Furthermore, most of the known oncogenic drivers upregulate nucleotide biosynthetic capacity, suggesting that this phenotype is a prerequisite for cancer initiation and progression. Despite the wealth of data demonstrating the efficacy of nucleotide synthesis inhibitors in preclinical cancer models and the well-established clinical use of these drugs in certain cancer settings, the full potential of these agents remains unrealized. In this Review, we discuss recent studies that have generated mechanistic insights into the diverse biological roles of hyperactive cancer cell nucleotide metabolism. We explore opportunities for combination therapies that are highlighted by these recent advances and detail key questions that remain to be answered, with the goal of informing urgently warranted future studies.

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“…Of note, genetic inhibition Epithelial intrinsic models of intestinal epithelial injury. Multiple models of intestinal epithelial injury and repair/regeneration were used, including DSS-, irradiation-, and 5FU-induced injuries (26,(70)(71)(72).…”

Section: Methodsmentioning

confidence: 99%

Claudin-2 protects against colitis-associated cancer by promoting colitis-associated mucosal healing

Ahmad,

Kumar,

Thapa

et al. 2023

Journal of Clinical Investigation

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Patients with inflammatory bowel disease (IBD) are susceptible to colitis-associated cancer (CAC). Chronic inflammation promotes the risk for CAC. In contrast, mucosal healing predicts improved prognosis in IBD and reduced risk of CAC. However, the molecular integration among colitis, mucosal healing, and CAC remains poorly understood. Claudin-2 (CLDN2) expression is upregulated in IBD; however, its role in CAC is not known. The current study was undertaken to examine the role for CLDN2 in CAC. The AOM/DSS-induced CAC model was used with WT and CLDN2-modified mice. High-throughput expression analyses, murine models of colitis/recovery, chronic colitis, ex vivo crypt culture, and pharmacological manipulations were employed in order to increase our mechanistic understanding. The Cldn2 KO mice showed significant inhibition of CAC despite severe colitis compared with WT littermates. Cldn2 loss also resulted in impaired recovery from colitis and increased injury when mice were subjected to intestinal injury by other methods. Mechanistic studies demonstrated a possibly novel role of CLDN2 in promotion of mucosal healing downstream of EGFR signaling and by regulation of Survivin expression. An upregulated CLDN2 expression protected from CAC and associated positively with crypt regeneration and Survivin expression in patients with IBD. We demonstrate a potentially novel role of CLDN2 in promotion of mucosal healing in patients with IBD and thus regulation of vulnerability to colitis severity and CAC, which can be exploited for improved clinical management.

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MnTE-2-PyP protects fibroblast mitochondria from hyperglycemia and radiation exposure

Cited by 7 publications

References 77 publications

Energy stress modulation of AMPK/FoxO3 signaling inhibits mitochondria-associated ferroptosis

Energy stress modulation of AMPK/FoxO3 signaling inhibits mitochondria-associated ferroptosis

Nucleotide metabolism: a pan-cancer metabolic dependency

Claudin-2 protects against colitis-associated cancer by promoting colitis-associated mucosal healing

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