PrPC displays an essential protective role from oxidative stress in an astrocyte cell line derived from PrPC knockout mice

Bertuchi, Fernanda R.; Bourgeon, Dominique; Landemberger, Michele Christine; Martins, Vilma R.; Cerchiaro, Giselle

doi:10.1016/j.bbrc.2011.12.098

Cited by 37 publications

(22 citation statements)

References 41 publications

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“…For example, basal levels of ROS and lipid peroxidation were lower in PrP C -transfected neuroblastoma and epithelial cell lines compared with untransfected controls (Rachidi et al, 2003; Zeng et al, 2003). Moreover, PrP C expression by primary neurons, astrocytes and cell lines has been associated with lower levels of damage following exposure to various oxidative toxins (Brown et al, 1997b, 2002; Anantharam et al, 2008; Dupiereux et al, 2008; Bertuchi et al, 2012). A possible mechanism is that PrP C modulates the activities of the antioxidant enzymes that convert ROS into less toxic products—several studies have shown lower superoxide dismutase and glutathione peroxidase activities in the absence of PrP C expression (Brown et al, 1997b; Miele et al, 2002; Rachidi et al, 2003; Sakudo et al, 2003; Paterson et al, 2008).…”

Section: Prpc Functionmentioning

confidence: 99%

Physiological Functions of the Cellular Prion Protein

Castle

Gill

2017

Front. Mol. Biosci.

154

153

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The prion protein, PrPC, is a small, cell-surface glycoprotein notable primarily for its critical role in pathogenesis of the neurodegenerative disorders known as prion diseases. A hallmark of prion diseases is the conversion of PrPC into an abnormally folded isoform, which provides a template for further pathogenic conversion of PrPC, allowing disease to spread from cell to cell and, in some circumstances, to transfer to a new host. In addition to the putative neurotoxicity caused by the misfolded form(s), loss of normal PrPC function could be an integral part of the neurodegenerative processes and, consequently, significant research efforts have been directed toward determining the physiological functions of PrPC. In this review, we first summarise important aspects of the biochemistry of PrPC before moving on to address the current understanding of the various proposed functions of the protein, including details of the underlying molecular mechanisms potentially involved in these functions. Over years of study, PrPC has been associated with a wide array of different cellular processes and many interacting partners have been suggested. However, recent studies have cast doubt on the previously well-established links between PrPC and processes such as stress-protection, copper homeostasis and neuronal excitability. Instead, the functions best-supported by the current literature include regulation of myelin maintenance and of processes linked to cellular differentiation, including proliferation, adhesion, and control of cell morphology. Intriguing connections have also been made between PrPC and the modulation of circadian rhythm, glucose homeostasis, immune function and cellular iron uptake, all of which warrant further investigation.

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Section: Prpc Functionmentioning

confidence: 99%

Physiological Functions of the Cellular Prion Protein

Castle

Gill

2017

Front. Mol. Biosci.

154

153

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“…Moreover, astrocytic PrP c expression appears to be important for reduction of hydrogen peroxide toxicity (Bertuchi et al, 2012), a reactive oxygen species whose production in mammalian cells is stimulated by hypoxia (Moller, 2001). …”

Section: Prpc-mediated Neuroprotection Against Hypoxiamentioning

confidence: 99%

Cellular Prion Protein (PrPc) and Hypoxia: True to Each Other in Good Times and in Bad, in Sickness, and in Health

Ramljak¹,

Herlyn

Zerr

2016

Front. Cell. Neurosci.

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The cellular prion protein (PrPc) and hypoxia appear to be tightly intertwined. Beneficial effects of PrPc on neuronal survival under hypoxic conditions such as focal cerebral ischemia are strongly supported. Conversely, increasing evidence indicates detrimental effects of increased PrPc expression on cancer progression, another condition accompanied by low oxygen tensions. A switch between anaerobic and aerobic metabolism characterizes both conditions. A cellular process that might unite both is glycolysis. Putative role of PrPc in stimulation of glycolysis in times of need is indeed thought provoking. A significance of astrocytic PrPc expression for neuronal survival under hypoxic conditions and possible association of PrPc with the astrocyte-neuron lactate shuttle is considered. We posit PrPc-induced lactate production via transactivation of lactate dehydrogenase A by hypoxia inducible factor 1α as an important factor for survival of both neurons and tumor cells in hypoxic microenvironment. Concomitantly, we discuss a cross-talk between Wnt/β-catenin and PI3K/Akt signaling pathways in executing PrPc-induced activation of glycolysis. Finally, we would like to emphasize that we see a great potential in joining expertise from both fields, neuroscience and cancer research in revealing the mechanisms underlying hypoxia-related pathologies. PrPc may prove focal point for future research.

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“…PrP c acted as a radical scavenger in both ROS-rich solution and astrocytes cultures in vitro, and its activity was essential in their protection against oxidative stress. This feature may reflect its protective functions in conditions similar to those observed during neurodegeneration and ischemia [5]. Another defensive mechanism is associated with the ability of PrP c to bind co-chaperon molecule, called stress-inducible protein 1 (STI1).…”

Section: Prion Proteinmentioning

confidence: 99%