Mitochondrial Dysfunction Due to Lack of Manganese Superoxide Dismutase Promotes Hepatocarcinogenesis

Konzack, Anja; Jakupovic, Mirza; Kubaichuk, Kateryna; Görlach, Agnes; Dombrowski, Frank; Miinalainen, Ilkka; Sormunen, Raija; Kietzmann, Thomas

doi:10.1089/ars.2015.6318

Cited by 24 publications

(24 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, the combination of SOD2 and cisplatin significantly inhibited ovarian tumor growth by inducing apoptosis 19 . In hepatoma cells, inhibition of SOD2 promoted tumorigenesis and produced a more malignant phenotype with metabolic transformation via a reduction β‐catenin and hypoxia‐inducible factor‐1α 20 . Serum expression of hepatocarcinogenesis markers was enhanced in mice deficient for hepatocyte‐specific SOD2 20 .…”

Section: Introductionmentioning

confidence: 99%

Redox regulation by SOD2 modulates colorectal cancer tumorigenesis through AMPK‐mediated energy metabolism

Zhou

Lyu

Miao

et al. 2020

Molecular Carcinogenesis

View full text Add to dashboard Cite

Colorectal cancer (CRC) is a common malignancy. Many reports have implicated aberrant mitochondrial activity in the progression of CRC, with particular emphasis on the dysregulation of redox signaling and oxidative stress. In this study, we focused on manganese superoxide dismutase (MnSOD/SOD2), a key antioxidant enzyme, which maintains intracellular redox homeostasis. Current literature presents conflicting mechanisms for how SOD2 influences tumorigenesis and tumor progression. Here, we explored the role of SOD2 in CRC specifically. We found high levels of SOD2 expression in CRC tissues. We carried out a series of experiments to determine whether knockdown of SOD2 expression in CRC cell lines would reverse features of tumorigenesis. We found that reduced SOD2 expression decreased cell proliferation, migration, and invasion activity in CRC cells. Results from an additional series of experiments on mitochondrial function implicated a dual role for SOD2 in promoting CRC progression. First, proper level of SOD2 helped CRC cells maintain mitochondrial function by disposal of superoxide (O2.−). Second, over‐expression of SOD2 induced H2O2‐mediated tumorigenesis by upregulating AMPK and glycolysis. Our results indicate that SOD2 may promote the occurrence and development of CRC by regulating the energy metabolism mediated by AMPK signaling pathways.

show abstract

Section: Introductionmentioning

confidence: 99%

Redox regulation by SOD2 modulates colorectal cancer tumorigenesis through AMPK‐mediated energy metabolism

Zhou

Lyu

Miao

et al. 2020

Molecular Carcinogenesis

View full text Add to dashboard Cite

show abstract

“…Indeed, hepatocyte-specific deletion of manganese superoxide dismutase (MnSOD; sod2 ) which generates H 2 O 2 , caused a disruption of the zonal gene expression [156]. Further, HIF-1α as well as β-catenin were absent in hepatocyte-specific MnSOD-deficient mice which were also more prone to chemically-induced carcinogenesis [157].…”

Section: Hypoxia Hifs and β-Catenin Signaling: A New Liaisonmentioning

confidence: 99%

Metabolic zonation of the liver: The oxygen gradient revisited

2017

Self Cite

View full text Add to dashboard Cite

The liver has a multitude of functions which are necessary to maintain whole body homeostasis. This requires that various metabolic pathways can run in parallel in the most efficient manner and that futile cycles are kept to a minimum. To a large extent this is achieved due to a functional specialization of the liver parenchyma known as metabolic zonation which is often lost in liver diseases. Although this phenomenon is known for about 40 years, the underlying regulatory pathways are not yet fully elucidated. The physiologically occurring oxygen gradient was considered to be crucial for the appearance of zonation; however, a number of reports during the last decade indicating that β-catenin signaling, and the hedgehog (Hh) pathway contribute to metabolic zonation may have shifted this view. In the current review we connect these new observations with the concept that the oxygen gradient within the liver acinus is a regulator of zonation. This is underlined by a number of facts showing that the β-catenin and the Hh pathway can be modulated by the hypoxia signaling system and the hypoxia-inducible transcription factors (HIFs). Altogether, we provide a view by which the dynamic interplay between all these pathways can drive liver zonation and thus contribute to its physiological function.

show abstract

“…The significance of maintaining the homeostasis of essential microelements cannot be overrated, considering the participation of iron and copper in the development of diseases of this organ [15,16], the role of manganese superoxide dismutase in liver tumour suppression [17], or the protective effect of zinc in the case of hepatoxicity of lithium [12]. Additionally, the necessity of maintaining the proper liver functions must be highlighted, considering that lithium therapy in psychiatric subjects is usually used for some years [4].…”

Section: Discussionmentioning

confidence: 99%

Homeostasis of chosen microelements in liver of rats receiving lithium and/or selenium orally

Kiełczykowska¹,

Kopciał²,

Marzec³

et al. 2017

J Pre Clin Clin Res.

View full text Add to dashboard Cite

Introduction and objective. Lithium and selenium have been the subjects of extensive research for many years. Concern about the physiological action of these elements results from the application of lithium in medicine, as well as the beneficial influence of selenium supplementation in different pathological states. However, little data are available concerning their effect on the homeostasis of essential microelements in organs. Therefore, the aim of the current study was to evaluate the influence of lithium and/or selenium administration on homeostasis of iron, zinc, copper and manganese in the liver of rats. Materials and method. The experiment was carried on 24 male Wistar rats (4 groups of 6 animals) subjected to the treatment with: group I (control) -saline; group II -lithium carbonate at a dose of 2.7 mg Li/kg b.w.; group III -sodium selenite at a dose of 0.5 mg Se/kg b.w.; group IV -both lithium carbonate and sodium selenite at the doses mentioned above. Administration was performed for 6 weeks, once a day by stomach tube, in the form of water solutions. Results. The tissue content of zinc, iron and manganese showed no statistical differences among the studied groups. Zn was slightly decreased in group III vs. control and group II. Fe was insignificantly enhanced in groups II and IV vs. control. Mn in group IV was slightly increased vs. groups II and III. Cu in group III was significantly decreased vs. group IV and slightly depleted vs. groups I and II. Conclusion. With the exception of Cu in the Se-treated group, lithium and/or selenium did not affect the studied microelements' liver homeostasis in a significant way. These results may contribute to the knowledge of essential microelements homeostasis in human organisms undergoing lithium therapy, and/or selenium supplementation.

show abstract

Mitochondrial Dysfunction Due to Lack of Manganese Superoxide Dismutase Promotes Hepatocarcinogenesis

Cited by 24 publications

References 67 publications

Redox regulation by SOD2 modulates colorectal cancer tumorigenesis through AMPK‐mediated energy metabolism

Redox regulation by SOD2 modulates colorectal cancer tumorigenesis through AMPK‐mediated energy metabolism

Metabolic zonation of the liver: The oxygen gradient revisited

Homeostasis of chosen microelements in liver of rats receiving lithium and/or selenium orally

Contact Info

Product

Resources

About