Bcl-2 enhances Ca2+ signaling to support the intrinsic regenerative capacity of CNS axons

Jiao, Jianwei; Huang, Xiaodan; Feit-Leithman, Rachel Ann; Neve, Rachael L.; Snider, William D.; Dartt, Darlene A.; Chen, Dong Feng

doi:10.1038/sj.emboj.7600589

Cited by 98 publications

(73 citation statements)

References 39 publications

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“…Isolated RGCs were seeded in 24-well plates coated with poly-D-lysine (10 g/mL; Sigma-Aldrich) and laminin (10 g/mL; Sigma-Aldrich) and were cultured in neurobasal medium supplemented with B27 Serum Free Supplement as described previously. 42 To confirm cell identity, cultures were stained with the RGCspecific antibody Tuj-1. Cell viability in the presence of different concentrations of glutamate (0, 5, 7.5, and 10 mmol/L) was determined with a live/dead assay (Invitrogen).…”

Section: Examination Of Ngb Function In Purified Rgc Culturesmentioning

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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Section: Examination Of Ngb Function In Purified Rgc Culturesmentioning

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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“…differentiation, regeneration, autophagy). 59,60 A similar consideration holds true for the role of proapoptotic Bcl-2 family members in the regulation of mitochondrial morphology and dynamics. 61 Thus, whereas the link between Bak, Bax and Bik and components of the mitochondrial fission/fusion machinery 62,63 has been extensively characterized during cell death, it cannot be excluded that this interaction might as well account for apoptosis-unrelated changes in mitochondrial dynamics.…”

Section: Vital Functions Of Mitochondrial Death Effectorsmentioning

confidence: 99%

No death without life: vital functions of apoptotic effectors

et al. 2008

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As a result of the genetic experiments performed in Caenorhabditis elegans, it has been tacitly assumed that the core proteins of the 'apoptotic machinery' (CED-3, -4, -9 and EGL-1) would be solely involved in cell death regulation/execution and would not exert any functions outside of the cell death realm. However, multiple studies indicate that the mammalian orthologs of these C. elegans proteins (i.e. caspases, Apaf-1 and multidomain proteins of the Bcl-2 family) participate in cell death-unrelated processes. Similarly, loss-of-function mutations of ced-4 compromise the mitotic arrest of DNA-damaged germline cells from adult nematodes, even in a context in which the apoptotic machinery is inoperative (for instance due to mutations of egl-1 or ced-3). Moreover, EGL-1 is required for the activation of autophagy in starved nematodes. Finally, the depletion of caspaseindependent death effectors, such as apoptosis-inducing factor (AIF) and endonuclease G, provokes cell death-independent consequences, both in mammals and in yeast (Saccharomyces cerevisiae). These results corroborate the conjecture that any kind of protein that has previously been specifically implicated in apoptosis might have a phylogenetically conserved apoptosisunrelated function, most likely as part of an adaptive response to cellular stress.

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“…23 Actually, Bcl-2 itself might indirectly control microtubule dynamics via an Erk-dependent pathway, at least in certain cells. 24 In addition, there is evidence for direct interactions between Bcl-2 family members and proteins of the cytoskeleton, or scaffold proteins, such as paxillin. 25 Indeed, the Bcl-2 family appears to participate to multiple signalling pathways into the cell, independently of the apoptosis.…”

Section: Nrz Controls Gastrulation Via a Snail-1-dependent Pathwaymentioning

confidence: 99%

The zebrafish bcl-2 homologue Nrz controls development during somitogenesis and gastrulation via apoptosis-dependent and -independent mechanisms

et al. 2005

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Although the role of the b-cell lymphoma (Bcl)-2 family of apoptosis inhibitors is well documented in tumor cells and tissue morphogenesis, their role during the early development of vertebrates is unknown. Here, we characterize Nrz, a new Bcl-2-related inhibitor of apoptosis in zebrafish. Nrz is a mitochondrial protein, antagonizing the death-accelerator Bax. The nrz gene is mainly expressed during gastrulation and somitogenesis. The knockdown of nrz with antisense morpholinos leads to alterations of the somites, correlated with an increase in apoptosis. In addition, earlier during development, in the zebrafish gastrula, nrz knockdown results in an increase of snail-1 expression at the margin and frequent gastrulation arrest at the shield stage, independently of apoptosis. Together these data suggest that Nrz, in addition to its effect on apoptosis, contributes to cell movements during gastrulation by negatively regulating the expression of Snail-1, a transcription factor that controls cell adhesion.

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Bcl-2 enhances Ca2+ signaling to support the intrinsic regenerative capacity of CNS axons

Cited by 98 publications

References 39 publications

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

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

No death without life: vital functions of apoptotic effectors

The zebrafish bcl-2 homologue Nrz controls development during somitogenesis and gastrulation via apoptosis-dependent and -independent mechanisms

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