The Cellular and Subcellular Localization of Neuroglobin and Cytoglobin ‐ A Clue to Their Function?

Hankeln, Thomas; Wystub, Sylvia; Laufs, Tilmann; Schmidt, Marc; Gerlach, Frank; Saaler-Reinhardt, Sigrid; Reuss, Stefan; Burmester, Thorsten

doi:10.1080/15216540500037794

Cited by 71 publications

(73 citation statements)

References 43 publications

(79 reference statements)

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“…1C). The Ngb signals in Spalax neurons were basically identical in regional distribution and intensity to those obtained from mice (19,39). Immunofluorescence detection of Ngb did not differ between brains prepared from normoxic and hypoxic (5 h, 6% O 2 ) Spalax.…”

Section: Resultsmentioning

confidence: 51%

“…Alternatively, it may function as a scavenger of reactive oxygen or nitrogen species (ROS/RNS) (22,23) or protect cells from cytochrome c-induced apoptosis (24,25). Regardless of its ultimate role, there is conclusive evidence that Ngb localization is tightly linked to active oxidative metabolism and mitochondria (19,20). The highest Ngb level was found in the neuronal retina, which also has the highest O 2 -consuming rate in the body (20,26).…”

mentioning

confidence: 99%

“…The physiological functions of Ngb and Cygb are still uncertain. In most mammals, Ngb resides in neurons of the central and peripheral nervous systems, as well as in endocrine organs (18,19). Ngb may have an Mb-like role in supplying O 2 to the mitochondrial respiratory chain (18,20,21).…”

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confidence: 99%

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Neuroglobin, cytoglobin, and myoglobin contribute to hypoxia adaptation of the subterranean mole rat Spalax

Avivi

Gerlach²,

Joel³

et al. 2010

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

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122

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The subterranean mole rat Spalax is an excellent model for studying adaptation of a mammal toward chronic environmental hypoxia. Neuroglobin (Ngb) and cytoglobin (Cygb) are O 2 -binding respiratory proteins and thus candidates for being involved in molecular hypoxia adaptations of Spalax. Ngb is expressed primarily in vertebrate nerves, whereas Cygb is found in extracellular matrix-producing cells and in some neurons. The physiological functions of both proteins are not fully understood but discussed with regard to O 2 supply, the detoxification of reactive oxygen or nitrogen species, and apoptosis protection. Spalax Ngb and Cygb coding sequences are strongly conserved. However, mRNA and protein levels of Ngb in Spalax brain are 3-fold higher than in Rattus norvegicus under normoxia. Importantly, Spalax expresses Ngb in neurons and additionally in glia, whereas in hypoxia-sensitive rodents Ngb expression is limited to neurons. Hypoxia causes an approximately 2-fold downregulation of Ngb mRNA in brain of rat and mole rat. A parallel regulatory response was found for myoglobin (Mb) in Spalax and rat muscle, suggesting similar functions of Mb and Ngb. Cygb also revealed an augmented normoxic expression in Spalax vs. rat brain, but not in heart or liver, indicating distinct tissue-specific functions. Hypoxia induced Cygb transcription in heart and liver of both mammals, with the most prominent mRNA up-regulation (12-fold) in Spalax heart. Our data suggest that tissue globins contribute to the remarkable tolerance of Spalax toward environmental hypoxia. This is consistent with the proposed cytoprotective effect of Ngb and Cygb under pathological hypoxic/ischemic conditions in mammals.

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Section: Resultsmentioning

confidence: 51%

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confidence: 99%

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Neuroglobin, cytoglobin, and myoglobin contribute to hypoxia adaptation of the subterranean mole rat Spalax

Avivi

Gerlach²,

Joel³

et al. 2010

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

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122

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“…In vertebrates, four types of globins have been reported: hemoglobin (Hb) in red blood cell [23], myoglobin (Mb) in muscle [59,60], neuroglobin (Ngb) and cytoglobin (Cygb). Cygb is ubiquitously expressed [3,20], and is upregulated in rat heart and liver following hypoxia [49] or in brain by hypoxia [10]. When Cygb mRNA was knocked down by siRNA, cell death was increased upon hydrogen peroxide-treatment [35], suggesting that Cygb protects cells against oxidative stress.…”

Section: Cystatin B (Cstb)mentioning

confidence: 99%

Microarray Analysis of Gene Expression by Rhei Rhizoma Water Extracts in a Hypoxia Model of Cultured Neurons

Lee¹,

Song²,

Moon³

2009

Journal of Life Science

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In this study, we investigated the effect of Rhei Rhizoma (RR; 大黃) water extract on gene expression in a hypoxia model of cultured rat hippocampal neurons. RR water extract (2.5 μg/ml) was added to the culture media on day 10 in vitro (DIV10), and a hypoxic shock (2% O2/5% CO2 , 37 o C, 3 h) was given on DIV13. After maintaining the cultures in normoxia for 24 hr, total RNA was isolated and used for microarray analysis. The MA-plot indicated that most genes were up-or downregulated within 2-fold. There were more downregulated genes (725 ea) than upregulated ones (472 ea) when larger than Global M value 0.2 (i.e., ＞15% increase) or smaller than Global M value -0.2 (i.e., ＞15% decrease) were considered. Antiapoptosis genes such as Tegt (2.4-fold), Nfkb1 (2.4-fold) Veg (1.8-fold), Ngfr (1.6-fold) were upregulated, while pro-apoptosis genes such as Bad (-64%), Cstb (-66%) were downregulated. Genes for combating environmental stress (stress response genes) such as Defb3 (2.7-fold), Cygb (2.2-fold), Ahsg (2.18-fold), Alox5 (2-fold) were upregulated. Genes for cell proliferation (cell cycle-related genes) such as Erbb2 (1.84-fold), Mapk12 gene (1.8-fold) was upregulated. Therefore, RR water extracts upregulate many pro-survival genes while downregulating many pro-death genes. It is interpreted that these genes, in combination with other regulated genes, can promote neuronal survival in a stress such as hypoxia. [40,46]. Effects of RR on lowering serum cholesterol are attributed to rhein, which are transformed from anthranoids sennoside A and B by bacterial enzymes in large intestine [55]. Rhaponticin in the rhizome of RR has extensive anti-allergic and anti-thrombotic properties [46]. RR extracts decreased serum creatinine levels in diabetic patients with neuropathy and retinopathy [18].Studies on the nervous system are relatively scarce. It has been reported that RR improves memory ability. By comparing the effects of the Compound Tong Jiang Oral Liquid with Da Huang added (TJ) and Qi Yin Oral Liquid (QY) without Da Huang on senile persons' memory ability, Tian et al. [55] discovered that TJ improves senile persons' memory ability, in addition to shortened interval and duration of defecation. However, effects of RR on the nervous system are not studied at the cellular level. Previously, our laboratory reported that RR suppresses production of reactive oxygen species (ROS) and loss of mitochondrial membrane potential (MMP) in a hypoxia model of rat hippocampal neurons in culture [34]. Here, we report results of a microarray analysis on the expression of genes in hypoxia. Materials and MethodsPreparation of water-extracts of RR Rhei Rhizoma (RR; 大黃) was selected according to the Korean Pharmacopoeia and obtained from Dongguk University Oriental Hospital (Gyeongju, Korea). Distilled water was added to the RR powder and it was agitated for 4 hr at room temperature (RT) followed by overnight at 4 o C. After centrifugation (15,000 rpm, 15 min, RT), the supernatant was filter-sterilized (pore size 0.2 μm) and stored at -20 ...

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“…Antarctic icefishes (16 species) lack hemoglobin, and six of the species also lack Mb. Elucidation of the icefish Ngb structure may potentially shed light on the physiological function of Ngb, especially considering apparent Ngb localization in tissues of increased oxidative metabolism and mitochondrial activity (15). The highest Ngb level was found in the retina, which has the highest oxygen-consuming rate in the body (16).…”

Section: Introductionmentioning

confidence: 99%

Structure and dynamics of Antarctic fish neuroglobin assessed by computer simulations

Boron¹,

Russo²,

Boechi³

et al. 2011

IUBMB Life

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Neuroglobin (Ngb) is a heme protein, highly conserved along evolution, predominantly found in the nervous system. It is upregulated by hypoxia and ischemia and may have a neuroprotective role under hypoxic stress. Although many other roles have been proposed, the physiological function is still unclear. Antarctic icefishes lack hemoglobin and some species also lack myoglobin, but all have Ngb and thus may help the elucidation of Ngb function. We present the first theoretically derived structure of fish Ngb and describe its behavior using molecular dynamics simulations. Specifically, we sequenced and analyzed Ngbs from a colorless‐blooded Antarctic icefish species Chaenocephalus aceratus and a related red‐blooded species (Dissostichus mawsoni). Both fish Ngbs are 6‐coordinated but have some peculiarities that differentiate them from mammalian counterparts: they have extensions in the N and C termini that can interact with the EF loop, and a gap in the alignment that changes the CD‐region structure/dynamics that has been found to play a key role in human neuroglobin. Our results suggest that a single mutation between both fish Ngbs is responsible for significant difference in the behavior of the proteins. The functional role of these characteristics is discussed. © 2011 IUBMB IUBMB Life, 63(3): 206–213, 2011

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The Cellular and Subcellular Localization of Neuroglobin and Cytoglobin ‐ A Clue to Their Function?

Cited by 71 publications

References 43 publications

Neuroglobin, cytoglobin, and myoglobin contribute to hypoxia adaptation of the subterranean mole rat Spalax

Neuroglobin, cytoglobin, and myoglobin contribute to hypoxia adaptation of the subterranean mole rat Spalax

Microarray Analysis of Gene Expression by Rhei Rhizoma Water Extracts in a Hypoxia Model of Cultured Neurons

Structure and dynamics of Antarctic fish neuroglobin assessed by computer simulations

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