Searching for Neuroglobin's role in the brain

Nienhaus, Karin; Nienhaus, G. Ulrich

doi:10.1080/15216540601188538

Cited by 41 publications

(31 citation statements)

References 44 publications

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“…Other hypotheses concerning the neuroprotective mechanism of human Ngb have been reported (50,51). Initially, Ngb was suggested to be an O 2 storage protein similar to Mb (1).…”

Section: Discussionmentioning

confidence: 99%

Human Neuroglobin Functions as an Oxidative Stress-responsive Sensor for Neuroprotection

Watanabe

Takahashi

Uchida

et al. 2012

Journal of Biological Chemistry

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Background: Mammalian neuroglobin (Ngb) is involved in neuroprotection under oxidative stress conditions. Results: Only under oxidative stress, human Ngb was recruited to lipid rafts by interacting with flotillin-1 and suppressed the activation of G␣ i/o by acting as its guanine nucleotide dissociation inhibitor. Conclusion: Human Ngb acts as an intracellular oxidative stress-responsive sensor to protect against cell death. Significance: The neuroprotective mechanism of human Ngb was revealed.

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“…Other hypotheses concerning the neuroprotective mechanism of human Ngb have been reported (50,51). Initially, Ngb was suggested to be an O 2 storage protein similar to Mb (1).…”

Section: Discussionmentioning

confidence: 99%

Human Neuroglobin Functions as an Oxidative Stress-responsive Sensor for Neuroprotection

Watanabe

Takahashi

Uchida

et al. 2012

Journal of Biological Chemistry

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“…Neuroglobin may serve as an oxygen store/transporter, gas sensor, reactive oxygen species scavenger, and signal transduction modulator based on its ability to bind to O 2 , NO, H 2 O 2, and G-protein [3,6] . However, there has been no clear physiological function that can be assigned to Ngb until now.…”

Section: Discussionmentioning

confidence: 99%

“…It has also been proposed that Ngb functions as a nitric oxide (NO) or reactive oxygen species scavenger, oxygen sensor and signal transduction regulator [5,6] . Neuroglobin binds and reacts to NO and H 2 O 2 without cytotoxic ferryl protein generation [7] .…”

Section: Introductionmentioning

confidence: 99%

Silencing neuroglobin enhances neuronal vulnerability to oxidative injury by down-regulating 14-3-3γ

Zhou

Lai

et al. 2009

Acta Pharmacol Sin

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Aim: To explore the protective role and mechanism of endogenous neuroglobin (Ngb) in neuronal cells under oxidative stress. Methods: A stable N2a neuroblastoma cell line expressing the Ngb-siRNA plasmid (N2a/Ngb-siRNA) was established by neomycin screening. Reverse transcription (RT)-PCR and Western blot analysis were used to detect Ngb gene and protein levels. Hydrogen peroxide was used to induce oxidative stress in N2a cells. Cytotoxicity and cell viability were measured by lactate dehydrogenase (LDH) and WST-8 assays. Hoechst staining demonstrated that the quantity of apoptotic cells among N2a/Ngb-siRNA cells following hydrogen peroxide treatment significantly increased compared with controls. In N2a/Ngb-siRNA cells, the expression level of activated caspase-3 significantly increased, whereas the expression of 14-3-3γ decreased compared with that of N2a/vec cells. Transfection of 14-3-3γ plasmids significantly enhanced the viability of N2a/Ngb-siRNA cells following hydrogen peroxide treatment compared with vector controls. Conclusion: Ngb contributes to neuronal defensive machinery against oxidative injuries by regulating 14-3-3γ expression.

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“…16 NGB is reported to colocalize to the mitochondria 8 and to reversibly bind oxygen, likely to supply oxygen to neurons. 17 NGB has also been proposed to play a role in scavenging reactive oxygen species (ROS), 18 -20 modulating nitric oxide homeostasis 21 and serving as a hypoxia sensor and initiating a signal cascade 22,23 in neurons.…”

mentioning

confidence: 99%

Neuroglobin Is an Endogenous Neuroprotectant for Retinal Ganglion Cells against Glaucomatous Damage

Wei

Cho

et al. 2011

The American Journal of Pathology

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Neuroglobin (NGB), a newly discovered member of the globin superfamily, may regulate neuronal survival under hypoxia or oxidative stress. Although NGB is greatly expressed in retinal neurons, the biological functions of NGB in retinal diseases remain largely unknown. We investigated the role of NGB in an experimental model of glaucoma, a neurodegenerative disorder that usually involves elevation of intraocular pressure (IOP). Elevated IOP is thought to induce oxidative stress in retinal ganglion cells (RGCs), thereby causing RGC death and, eventually, blindness. We found that NGB plays a critical role in increasing RGC resistance to ocular hypertension and glaucomatous damage. Neuroglobin (NGB) is a novel member of the globin superfamily that is distantly related to hemoglobin and myoglobin. 1 A highly conserved protein in evolution, human and mouse Ngb, both comprised of 151 amino acids, are 94% identical. 2,3 In mammals, expression of NGB is found in the brain, retina, and other nerve tissues, predominantly in neurons but absent from glial cells. 4 -7 Distribution of NGB protein in the normal human retina is very similar to what has been described in mice: NGB is detected primarily in the plexiform layers and photoreceptor inner segments, which are rich in mitochondria and synapses and consume high amounts of oxygen. 8,9 NGB has been shown to act as an endogenous neuroprotective molecule that enhances neuronal survival under hypoxic-ischemic insults in the brain 10 -12 ; however, its physiological functions and molecular mode of actions are not fully understood. Of note, NGB is present at a 100-fold greater concentration in the retina than in the brain, 8,[13][14][15] suggesting that the retina may be its most important site of function; however, among the many unknown roles of NGB, functional significance of NGB expression in the retina has been largely unexplored.

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Searching for Neuroglobin's role in the brain

Cited by 41 publications

References 44 publications

Human Neuroglobin Functions as an Oxidative Stress-responsive Sensor for Neuroprotection

Human Neuroglobin Functions as an Oxidative Stress-responsive Sensor for Neuroprotection

Silencing neuroglobin enhances neuronal vulnerability to oxidative injury by down-regulating 14-3-3γ

Neuroglobin Is an Endogenous Neuroprotectant for Retinal Ganglion Cells against Glaucomatous Damage

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