Manganese superoxide dismutase activity regulates transitions between quiescent and proliferative growth

Sarsour, Ehab H.; Venkataraman, Sujatha; Kalen, Amanda L.; Oberley, Larry W.; Goswami, Prabhat C.

doi:10.1111/j.1474-9726.2008.00384.x

Cited by 128 publications

(166 citation statements)

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“…Several recent studies show a link between cellular metabolism and cell cycle progression (Mitra et al 2009;Sarsour et al 2010;Sarsour et al 2008;Venkatesha et al 2010;Wang et al 2006). Cyclin D1 and E coordinate cell cycle progression with mitochondrial metabolism and functions (Mitra et al 2009;Wang et al 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Cyclin D1 and E coordinate cell cycle progression with mitochondrial metabolism and functions (Mitra et al 2009;Wang et al 2006). Likewise, MnSOD dependent regulation of transition between quiescence and the proliferative cycle was associated with cyclin D1 and cyclin B1 protein levels (Sarsour et al 2008); absence of MnSOD activity negatively impacts mitochondrial morphology and functions, which inhibits quiescent NHFs entry into the proliferative cycle ). An inverse correlation was observed between cyclin D1 protein levels and glucose consumption in oxidatively stressed cells (Venkatesha et al 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Flow cytometry measurements of MitoSOX and MitoTracker fluorescence (Invitrogen) were performed to determine mitochondrial ROS levels in control and HT-treated NHFs Sarsour et al 2008). Monolayer cultures were incubated with Hanks buffered salt solution containing 10 μM MitoSOX and 0.5 μM MitoTracker green.…”

Section: Flow Cytometry Assaysmentioning

confidence: 99%

“…Total cellular protein extracts were assayed for MnSOD and CuZnSOD activities following a previously published gel-electrophoresis assay (Beauchamp and Fridovich 1971;Sarsour et al 2010;Sarsour et al 2008). Briefly, control and HT-treated NHFs were harvested by scraping the monolayers and cell pellets were resuspended in phosphate buffer (pH 7.8).…”

Section: Sod Activity Assaymentioning

confidence: 99%

“…Replication-deficient adenoviruses containing cytomegalovirus promoter driven dominant-negative mutant form of human MnSOD cDNA (Zhang et al 2006) were used to infect quiescent NHFs following our previously published method (Sarsour et al 2008). Site-directed mutagenesis was used to generate the mutant form of human MnSOD that has a histidine to leucine substitution at amino acid 26 (Zhang et al 2006).…”

Section: Adenoviral Infectionmentioning

confidence: 99%

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MnSOD activity regulates hydroxytyrosol-induced extension of chronological lifespan

Sarsour

Kumar

Kalen

et al. 2011

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Chronological lifespan (CLS) is defined as the duration of quiescence in which normal cells retain the capacity to reenter the proliferative cycle. This study investigates whether hydroxytyrosol (HT), a naturally occurring polyphenol found in olives, extends CLS in normal human fibroblasts (NHFs). Quiescent NHFs cultured for a long duration (30-60 days) lose their capacity to repopulate. Approximately 60% of these cells exit the cell cycle permanently; a significant increase in the doubling time of the cell population was observed. CLS was extended in quiescent NHFs that were cultured in the presence of HT for 30-60 days. HT-induced extension of CLS was associated with an approximately 3-fold increase in manganese superoxide dismutase (MnSOD) activity while there was no change in copper-zinc superoxide dismutase, catalase, or glutathione peroxidase protein levels. Quiescent NHFs overexpressing a dominant-negative mutant form of MnSOD failed to extend CLS. HT suppressed ageassociated increase in mitochondrial ROS levels. Results from spectroscopy assays indicate that HT in the presence of peroxidases can undergo catechol-semiquinone-quinone redox cycling generating superoxide, which in a cellular context can activate the antioxidant system, e.g., MnSOD expression. These results demonstrate that HT extends CLS by increasing MnSOD activity and decreasing age-associated mitochondrial reactive oxygen species accumulation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Flow Cytometry Assaysmentioning

confidence: 99%

Section: Sod Activity Assaymentioning

confidence: 99%

Section: Adenoviral Infectionmentioning

confidence: 99%

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MnSOD activity regulates hydroxytyrosol-induced extension of chronological lifespan

Sarsour

Kumar

Kalen

et al. 2011

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Upregulation of manganese superoxide dismutase (SOD2) is a common pathway for neuroendocrine differentiation in prostate cancer cells

Quiros

Sáinz

Hevia

et al. 2009

Intl Journal of Cancer

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Despite improvements in diagnosis of advanced prostate cancer (PCa), treatment is not efficient and 5-year survival is still low. Initially, the less abundant of cell types, neuroendocrine cells (NE), are involved in regulatory process but their physiological role is not fully understood. Among others, an increase in NE cells along with tumor progression has been commonly reported but their role in tumorigenesis or the molecular mechanisms of transdifferentiation is still a matter of debate. We have used human PCa cells (LNCaP) induced to differentiate to NE cells with several stimuli: androgen withdrawal, cyclic AMP or treatment with the antioxidant pineal hormone melatonin. PCa patients' specimens were also analyzed by western blotting and by immunocytochemistry. NE-like LNCaP cells express high levels of mitochondrial superoxide dismutase (MnSOD/SOD2) in addition to NE markers. MnSOD upregulation is mediated by NFjB transcription factor, mainly through p65 translocation into the nuclei. More importantly, overexpression of MnSOD induces the rise of NE-markers in LNCaP cells, showing that MnSOD upregulation might be instrumental for NE differentiation in PCa cells. Furthermore, MnSOD is highly expressed in advanced tumors of patients' when compared with control, nonpathological samples or with low-grade tumors, along with the presence of synaptophysin, a common NE marker. Also, fluorescence immunohistochemical analysis revealed that MnSOD colocalizes with NE markers in most of NE cells observed in PCa specimens. The present findings indicate that MnSOD is essential for NE transdifferentiation and mediates in part the differentiation process, which appears also to be critical in vivo. ' 2009 UICC

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Continuously generated H₂O₂stimulates the proliferation and osteoblastic differentiation of human periodontal ligament fibroblasts

Choe

Son

et al. 2012

J of Cellular Biochemistry

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Numerous studies have shown that hydrogen peroxide (H2O2) inhibits proliferation and osteoblastic differentiation in bone-like cells. Human periodontal ligament fibroblasts (PLF) are capable of differentiating into osteoblasts and are exposed to oxidative stress during periodontal inflammation. However, the cellular responses of PLF to H2O2 have not been identified. In this study, we examined how H2O2 affects the viability and proliferation of PLF by exposing the cells to glucose oxidase (GO) or direct addition of H2O2. We also explored the effects of GO on the osteoblastic differentiation of PLF and the mechanisms involved. The viability and proliferation in PLF were increased with the addition of 10 mU/ml GO but not by volumes greater than 15 mU/ml or by H2O2 itself. GO-stimulated DNA synthesis was correlated with the increase in cyclin E protein levels in the cells. Osteoblastic differentiation of PLF was also ugmented by combined treatment with GO, as evidenced by the increases in alkaline phosphatase activity, mineralization, collagen synthesis, and osteocalcin content in the cells. The inductions of runt-related transcription factor 2 and osterix mRNA and proteins were further increased in PLF incubated in combination with GO compared to those in untreated cells. These results demonstrate that the continuous presence of H2O2 stimulates the proliferation of PLF and augments their potential to differentiate into osteoblasts through the up-regulation of bone-specific transcription factors. Collectively, we suggest that H2O2 may elicit the functions of PLF in maintaining the dimensions of the periodontal ligament and in mediating a balanced metabolism in alveolar bone.

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Manganese superoxide dismutase activity regulates transitions between quiescent and proliferative growth

Cited by 128 publications

References 28 publications

MnSOD activity regulates hydroxytyrosol-induced extension of chronological lifespan

MnSOD activity regulates hydroxytyrosol-induced extension of chronological lifespan

Upregulation of manganese superoxide dismutase (SOD2) is a common pathway for neuroendocrine differentiation in prostate cancer cells

Continuously generated H₂O₂stimulates the proliferation and osteoblastic differentiation of human periodontal ligament fibroblasts

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Manganese superoxide dismutase activity regulates transitions between quiescent and proliferative growth

Cited by 128 publications

References 28 publications

MnSOD activity regulates hydroxytyrosol-induced extension of chronological lifespan

MnSOD activity regulates hydroxytyrosol-induced extension of chronological lifespan

Upregulation of manganese superoxide dismutase (SOD2) is a common pathway for neuroendocrine differentiation in prostate cancer cells

Continuously generated H2O2stimulates the proliferation and osteoblastic differentiation of human periodontal ligament fibroblasts

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Continuously generated H₂O₂stimulates the proliferation and osteoblastic differentiation of human periodontal ligament fibroblasts