Knockdown of Cytoglobin Expression Sensitizes Human Glioma Cells to Radiation and Oxidative Stress

Fang, Jingye; Ma, Ivy; Allalunis‐Turner, Joan

doi:10.1667/rr2517.1

Cited by 40 publications

(29 citation statements)

References 39 publications

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“…Our in vitro loss-and gain-of-function studies using C2C12 myoblasts reflect Cygb's ability to influence cellular redox signaling, with depletion of Cygb increasing ROS generation and sensitizing the cells to stress-induced apoptosis. These findings are consistent with similar loss-and gain-offunction studies demonstrating the ability of Cygb, Mb, or their neuron-specific relative neuroglobin to provide cytoprotection under conditions of oxidative stress (29)(30)(31)(32)(33)(34)(59)(60)(61)(62)(63)(64)(65)(66)(67)(68). Mutation of the heme-binding domain of Cygb disrupted its ability to confer protection in vitro, demonstrating that Cygb function in this context depends on this core protein structure, a feature common to all globin proteins, and not on a domain unique to Cygb.…”

Section: Discussionsupporting

confidence: 86%

Cytoglobin modulates myogenic progenitor cell viability and muscle regeneration

Singh¹,

Canseco²,

Manda³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Mammalian skeletal muscle can remodel, repair, and regenerate itself by mobilizing satellite cells, a resident population of myogenic progenitor cells. Muscle injury and subsequent activation of myogenic progenitor cells is associated with oxidative stress. Cytoglobin is a hemoprotein expressed in response to oxidative stress in a variety of tissues, including striated muscle. In this study, we demonstrate that cytoglobin is up-regulated in activated myogenic progenitor cells, where it localizes to the nucleus and contributes to cell viability. siRNA-mediated depletion of cytoglobin from C2C12 myoblasts increased levels of reactive oxygen species and apoptotic cell death both at baseline and in response to stress stimuli. Conversely, overexpression of cytoglobin reduced reactive oxygen species levels, caspase activity, and cell death. Mice in which cytoglobin was knocked out specifically in skeletal muscle were generated to examine the role of cytoglobin in vivo. Myogenic progenitor cells isolated from these mice were severely deficient in their ability to form myotubes as compared with myogenic progenitor cells from wild-type littermates. Consistent with this finding, the capacity for muscle regeneration was severely impaired in mice deficient for skeletal-muscle cytoglobin. Collectively, these data demonstrate that cytoglobin serves an important role in muscle repair and regeneration.

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Section: Discussionsupporting

confidence: 86%

Cytoglobin modulates myogenic progenitor cell viability and muscle regeneration

Singh¹,

Canseco²,

Manda³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…The antioxidant effects of CYGB have recently been investigated, and emerging evidence has demonstrated a protective role of CYGB against oxidative stress, especially in models of fibrosis that involve hypoxic reperfusion and subsequent oxidative injury (19, 25, 50 -53). It was also reported that CYGB expression protected neuronal cells from oxidative damage in vitro (21,22,54,55); however, it is unclear whether this is a direct antioxidative effect of CYGB under HI conditions. Downstream signaling in the CYGB pathway may result in these antioxidative effects.…”

Section: Discussionmentioning

confidence: 98%

“…oping and adult brain (20) and is protective under oxidative stress in cell lines (21,22). More recently, Cygb was found to act as a tumor suppressor gene (23,24), and protect kidney fibroblasts under ischemic conditions (25), which are related to oxidative stress (25)(26)(27).…”

mentioning

confidence: 99%

Mechanisms of Neuroprotection from Hypoxia-Ischemia (HI) Brain Injury by Up-regulation of Cytoglobin (CYGB) in a Neonatal Rat Model

Tian

Yang

Xiao

et al. 2013

Journal of Biological Chemistry

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Background: Potential functions of cytoglobin (CYGB) in neonatal hypoxia-ischemia (HI) brain injury have not been reported. Results: Up-regulation of CYGB reduces HI injury and improves long term cognitive impairment after neonatal HI. Conclusion: CYGB exhibits neuroprotective effects, possibly through antioxidant and antiapoptotic functions as well as by stimulating angiogenesis. Significance: These results provide a novel target for developing a clinically relevant strategy for future studies.

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“…We have previously reported that Ngb and Cygb are expressed in human GBM cell lines (18)(19)(20), as well as in human primary tumors including brain tumors (19). In this study, we examined whether hemoglobins (α, β, γ, δ, ζ and ε) are also expressed in human GBM cell lines.…”

Section: Introductionmentioning

confidence: 99%

Adult, embryonic and fetal hemoglobin are expressed in human glioblastoma cells

Emara

Turner

Allalunis‐Turner

2013

International Journal of Oncology

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Hemoglobin is a hemoprotein, produced mainly in erythrocytes circulating in the blood. However, non-erythroid hemoglobins have been previously reported in other cell types including human and rodent neurons of embryonic and adult brain, but not astrocytes and oligodendrocytes. Human glioblastoma multiforme (GBM) is the most aggressive tumor among gliomas. However, despite extensive basic and clinical research studies on GBM cells, little is known about glial defence mechanisms that allow these cells to survive and resist various types of treatment. We have shown previously that the newest members of vertebrate globin family, neuroglobin (Ngb) and cytoglobin (Cygb), are expressed in human GBM cells. In this study, we sought to determine whether hemoglobin is also expressed in GBM cells. Conventional RT-PCR, DNA sequencing, western blot analysis, mass spectrometry and fluorescence microscopy were used to investigate globin expression in GBM cell lines (M006x, M059J, M059K, M010b, U87R and U87T) that have unique characteristics in terms of tumor invasion and response to radiotherapy and hypoxia. The data showed that α, β, γ, δ, ζ and ε globins are expressed in all tested GBM cell lines. To our knowledge, we are the first to report expression of fetal, embryonic and adult hemoglobin in GBM cells under normal physiological conditions that may suggest an undefined function of those expressed hemoglobins. Together with our previous reports on globins (Ngb and Cygb) expression in GBM cells, the expression of different hemoglobins may constitute a part of series of active defence mechanisms supporting these cells to resist various types of treatments including chemotherapy and radiotherapy.

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Knockdown of Cytoglobin Expression Sensitizes Human Glioma Cells to Radiation and Oxidative Stress

Cited by 40 publications

References 39 publications

Cytoglobin modulates myogenic progenitor cell viability and muscle regeneration

Cytoglobin modulates myogenic progenitor cell viability and muscle regeneration

Mechanisms of Neuroprotection from Hypoxia-Ischemia (HI) Brain Injury by Up-regulation of Cytoglobin (CYGB) in a Neonatal Rat Model

Adult, embryonic and fetal hemoglobin are expressed in human glioblastoma cells

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