The Cu–Zn superoxide dismutase (SOD1) inhibits ERK phosphorylation by muscarinic receptor modulation in rat pituitary GH3 cells

Secondo, Agnese; Mizio, Mariarosaria De; L, Zirpoli; Santillo, Mariarosaria; Mondola, Paolo

doi:10.1016/j.bbrc.2008.08.110

Cited by 16 publications

(17 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Differences in SOD1 neuroprotection against different toxic stimuli are in line with previous works that have or have not found neuroprotective effects of SOD1 in nonconditioned media, sometimes using very high amounts of exogenously added protein [60,61,62,63,64,65,66]. To further complicate this situation, it has to be considered that SOD1 may act on target cells both through its catalytic activity and through receptor interaction [46,47]. In the present study, we started to characterize the mechanism of neuroprotection mediated through SOD1.…”

Section: Discussionsupporting

confidence: 59%

“…In view of previous evidence that released SOD1 could regulate cellular calcium levels in a paracrine way through receptor-mediated interactions in neuroblastoma cells [45,46,47], we sought to analyze the involvement of a similar mechanism in the neuroprotective action of the protein and of the conditioned medium containing it. To this end, a microfluorometric analysis of intracellular calcium dynamics was performed in 2 m M [Ca 2+ ] o by measuring changes in the fluorescence emission ratio of fura-2-loaded CGNs.…”

Section: Resultsmentioning

confidence: 99%

“…By decreasing the Cu 2+ loading on SOD1, these inhibitors not only interfere with its enzymatic activity but also affect SOD1 structure and dimerization [79]. As a result, in agreement with the lack of an SOD1 mimetic neuroprotective effect, the inhibitor-mediated reduction of both exogenous SOD1 and MCM neuroprotection could be determined by a possible change in SOD1 structure due to Cu 2+ chelation and by the consequent alteration of SOD1 interactions with receptors [45,46,47]. …”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Copper-Zinc Superoxide Dismutase (SOD1) Is Released by Microglial Cells and Confers Neuroprotection against 6-OHDA Neurotoxicity

Polazzi¹,

Mengoni²,

Caprini

et al. 2012

Neurosignals

7,257

View full text Add to dashboard Cite

Microglial-neuronal interactions are essential for brain physiopathology. In this framework, recent data have changed the concept of microglia from essentially macrophagic cells to crucial elements in maintaining neuronal homeostasis and function through the release of neuroprotective molecules. Using proteomic analysis, here we identify copper-zinc superoxide dismutase (SOD1) as a protein produced and released by cultured rat primary microglia. Evidence for a neuroprotective role of microglia-derived SOD1 resulted from experiments in which primary cerebellar granule neurons (CGNs) were exposed to the dopaminergic toxin 6-hydroxydopamine (6-OHDA). Microglial conditioned medium, in which SOD1 had accumulated, protected CGNs from degeneration, and neuroprotection was abrogated by SOD1 inhibitors. These effects were replicated when exogenous SOD1 was added to a nonconditioned medium. SOD1 neuroprotective action was mediated by increased cell calcium from an external source. Further experiments demonstrated the specificity of SOD1 neuroprotection against 6-OHDA compared to other types of neurotoxic challenges. SOD1, constitutively produced and released by microglia through a lysosomal secretory pathway, is identified here for the first time as an essential component of neuroprotection mediated by microglia. This novel information is relevant to stimulating further studies of microglia-mediated neuroprotection in in vivo models of neurodegenerative diseases.

show abstract

Section: Discussionsupporting

confidence: 59%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Copper-Zinc Superoxide Dismutase (SOD1) Is Released by Microglial Cells and Confers Neuroprotection against 6-OHDA Neurotoxicity

Polazzi¹,

Mengoni²,

Caprini

et al. 2012

Neurosignals

7,257

View full text Add to dashboard Cite

show abstract

“…8), are compatible with recent findings that Cu-Zn superoxide dismutase (SOD1) inhibits ERK phosphorylation in pituitary GH3 cells. 38 With reference to the mitogen-activated protein kinase pathway, it has been proposed as a specific molecular tumor target 1-3 based on the frequent constitutive ERK activation in cancer cells. 1,2 However, the MAP/ERK pathway can either stimulate or inhibit DNA synthesis depending upon whether its activation is acute/phasic or chronic.…”

Section: Discussionmentioning

confidence: 99%

ERK activation increases nitroprusside induced apoptosis in human melanoma cells irrespective of p53 status: Role of superoxide dismutases

Gomez-Sarosi¹,

Strasberg–Rieber²,

Rieber³

2009

Cancer Biology & Therapy

View full text Add to dashboard Cite

Constitutive ERK activation, superoxide dismutases (SOD) and p53 mutations are implicated in modulating tumor apoptotic response. We now investigated whether human melanoma survival in response to sodium nitroprusside (SNP) is modulated by: (a) stable introduction of a DN-mutant p53; (b) pharmacologically inhibiting ERK activation with UO126; (c) addition of exogenous SOD. Nitroprusside releases nitric oxide (NO) when intact, or acts in a NO-independent manner via iron and residual cyanide after light exposure (lex-SNP). When tested at 300 μM in 72 h treatments by cytometric live-dead assays, intact SNP caused a 50% lethality versus a 30% lethality induced by lex-SNP. No protection from SNP toxicity was seen when inhibiting the PI3-kinase pathway with LY294002 or c-Jun NH 2 kinase signaling with SP600125. However, pretreatment with UO126 protected from SNP-mediated cell death including counteracting apoptosis-associated Bax expression and PARP cleavage, plus reversing loss of Cu,Zn-SOD. Moreover, addition of exogenous SOD also protected cells from SNP toxicity. In spite of the greater earlier effects of intact SNP, cells treated with single doses of either intact or lex-SNP, revealed about a 90% mortality in longer 120 h treatments, and these were also counteracted by UO126 or exogenous SOD. This report is the first to show that: constitutive ERK activation characteristic of cancer cells, increases a nitroprusside-induced apoptosis modulated by SOD.

show abstract

“…To identify additional mechanisms important for MPK-1 activity, we focused on ROS, which have been implicated in regulating MAPK in cultured cells (Abe et al, 2000; Aikawa et al, 1997; Secondo et al, 2008). The Cu/Zn superoxide dismutase SOD-1 converts ROS to oxygen or hydrogen peroxide.…”

Section: Resultsmentioning

confidence: 99%

MSP hormonal control of the oocyte MAP kinase cascade and reactive oxygen species signaling

Yang

Han

Miller

2010

Developmental Biology

View full text Add to dashboard Cite

The MSP domain is a conserved immunoglobulin-like structure that is important for C. elegans reproduction and human motor neuron survival. C. elegans MSPs are the most abundant proteins in sperm, where they function as intracellular cytoskeletal proteins and secreted hormones. Secreted MSPs bind to multiple receptors on oocyte and ovarian sheath cell surfaces to induce oocyte maturation and sheath contraction. MSP binding stimulates oocyte MPK-1 ERK MAP Kinase (MAPK) phosphorylation, but the function and mechanism are not well understood. Here we show that the Shp class protein-tyrosine phosphatase PTP-2 acts in oocytes downstream of sheath/oocyte gap junctions to promote MSP-induced MPK-1 phosphorylation. PTP-2 functions in the oocyte cytoplasm, not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation. We also provide evidence that MSP promotes production of reactive oxygen species (ROS), which act as second messengers to augment MPK-1 phosphorylation. The Cu/Zn superoxide dismutase SOD-1, an enzyme that catalyzes ROS breakdown in the cytoplasm, inhibits MPK-1 phosphorylation downstream of or in parallel to ptp-2. Our results support the model that MSP triggers PTP-2/Ras activation and ROS production to stimulate MPK-1 activity essential for oocyte maturation. We propose that secreted MSP domains and Cu/Zn superoxide dismutases function antagonistically to control ROS and MAPK signaling.

show abstract

The Cu–Zn superoxide dismutase (SOD1) inhibits ERK phosphorylation by muscarinic receptor modulation in rat pituitary GH3 cells

Cited by 16 publications

References 15 publications

Copper-Zinc Superoxide Dismutase (SOD1) Is Released by Microglial Cells and Confers Neuroprotection against 6-OHDA Neurotoxicity

Copper-Zinc Superoxide Dismutase (SOD1) Is Released by Microglial Cells and Confers Neuroprotection against 6-OHDA Neurotoxicity

ERK activation increases nitroprusside induced apoptosis in human melanoma cells irrespective of p53 status: Role of superoxide dismutases

MSP hormonal control of the oocyte MAP kinase cascade and reactive oxygen species signaling

Contact Info

Product

Resources

About