Interaction between the Alzheimer's survival peptide humanin and insulin-like growth factor-binding protein 3 regulates cell survival and apoptosis

Ikonen, Maaria; Liu, Bing-Rong; Hashimoto, Yuichi; Ma, Liqun; Lee, Kuk‐Wha; Niikura, Takako; Nishimoto, Ikuo; Cohen, Pinchas

doi:10.1073/pnas.2135111100

Cited by 253 publications

(263 citation statements)

References 31 publications

(53 reference statements)

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“…Cell viability was calculated by measuring the activity of dehydrogenase in living cells with a WST-8 assay [26] . Both N2a/Ngb-siRNA and N2a/vec cells showed a concentrationdependent decrease in cell viability following H 2 O 2 treatment (Figure 2A).…”

Section: Resultsmentioning

confidence: 99%

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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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Section: Resultsmentioning

confidence: 99%

“…An LDH assay was performed using a kit (Promega, USA). The WST-8 cell viability assay was performed using a Cell Counting Kit-8 (CCK-8) (Dojindo Laboratories, Japan) [26] . The absorbance for the LDH and WST-8 assays was determined at 492 nm and 450 nm, respectively, using a microtiter plate reader (Synergy 2, BioTek, USA).…”

Section: Cytotoxicity Assaysmentioning

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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Section: Introductionmentioning

confidence: 99%

“…[4][5][6][7][8] It may also have IGF-independent antitumor activities through cell-surface or intracellular protein interaction, its nuclear translocation, or its transcriptional regulation. 7,[9][10][11][12] However, the mechanisms that mediate IGFBP-3's IGF-independent antitumor activity have not been clearly defined.The 82-kDa phosphoprotein transcription factor early growth response protein 1 (Egr-1), an immediate early gene product, has been implicated in multiple cellular processes, including cell growth, apoptosis, wound healing, and angiogenesis. Mitogenic stimuli, including serum, PDGF, peptide growth factors, and B-Raf, and nonmitogenic stresses, including ␥-irradiation and hypoxia, activate Egr-1 expression through serum response elements (SREs) in the Egr-1 promoter, where serum response factor (SRF) and ternary complex factors form transcriptionally active ternary complexes.…”

mentioning

confidence: 99%

Antiangiogenic antitumor activities of IGFBP-3 are mediated by IGF-independent suppression of Erk1/2 activation and Egr-1–mediated transcriptional events

Kim

Choi

Lee

et al. 2011

Blood

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Most antiangiogenic therapies currently being evaluated in clinical trials target the vascular endothelial growth factor pathway; however, the tumor vasculature can acquire resistance to vascular endothelial growth factor-targeted therapy by shifting to other angiogenesis mechanisms. Insulin-like growth factor binding protein-3 (IGFBP-3) has been reported to suppress tumor growth and angiogenesis by both IGF-dependent and IGFindependent mechanisms; however, understanding of its IGF-independent mechanisms is limited. We observed that IGFBP-3 blocked tumor angiogenesis and growth in non-small cell lung cancer and head and neck squamous cell carcinoma. Conditioned media from an IGFBP-3-treated non-small cell lung cancer cell line displayed a significantly decreased capacity to induce HUVEC proliferation and aortic sprouting. In cancer cells, IGFBP-3 directly interacted with Erk1/2, leading to inactivation of Erk1/2 and Elk-1, and suppressed transcription of early growth response protein 1 and its target genes, basic fibroblast growth factor and platelet-derived growth factor. These data suggest that IGF-independent Erk1/2 inactivation and decreased IGFBP-3-induced Egr-1 expression block the autocrine and paracrine loops of angiogenic factors in vascular endothelial and cancer cells. Together, these findings provide a molecular framework of IGFBP-3's IGF-independent antiangiogenic antitumor activities. IntroductionAngiogenesis, the formation of new capillaries from existing blood vessels, is essential to carcinogenic processes, including solid tumor formation, growth, invasion, and metastasis. 1 Most tumors can stimulate angiogenesis by switching on the production of numerous cytokines and growth factors, including fibroblast growth factors (FGFs), vascular endothelial growth factors (VEGFs), and platelet-derived growth factors (PDGFs). 2 Several antiangiogenic agents are in various phases of clinical trials for human cancer; however, most of these agents target the VEGF signaling pathway. 3 Therefore, other potential therapeutic agents that block non-VEGF angiogenic pathways need to be evaluated.Insulin-like growth factor-binding protein-3 (IGFBP-3), a member of a family of 6 IGFBPs, has demonstrated antiproliferative, proapoptotic, antiangiogenic, and antimetastatic activity in a variety of cancer cells. [4][5][6][7][8] It may also have IGF-independent antitumor activities through cell-surface or intracellular protein interaction, its nuclear translocation, or its transcriptional regulation. 7,[9][10][11][12] However, the mechanisms that mediate IGFBP-3's IGF-independent antitumor activity have not been clearly defined.The 82-kDa phosphoprotein transcription factor early growth response protein 1 (Egr-1), an immediate early gene product, has been implicated in multiple cellular processes, including cell growth, apoptosis, wound healing, and angiogenesis. Mitogenic stimuli, including serum, PDGF, peptide growth factors, and B-Raf, and nonmitogenic stresses, including ␥-irradiation and hypoxia, activate Egr-1 expre...

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“…HN suppresses the neurotoxicity of various causative genes for familial AD (FAD) including FAD-related mutant PS1 and PS2 genes [17][18][19] , and inhibits the neuronal cell death caused by Aβ [20,21] . HN is also effective against cell death caused by non-AD-related insults, such as serum deprivation, prion peptide 118-135, and insulin-like growth factor binding protein 3 [22][23][24] . However, the neuroprotective effects and mechanism(s) of action of HN on Aβ-induced AD-like pathological changes and memory defi cits in vivo are still not fully described.…”

Section: Introductionmentioning

confidence: 99%

Humanin attenuates Alzheimer-like cognitive deficits and pathological changes induced by amyloid β-peptide in rats

Chai

Duan

et al. 2014

Neurosci. Bull.

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Amyloid β-peptide (Aβ) has been implicated as a key molecule in the neurodegenerative cascades of Alzheimer's disease (AD). Humanin (HN) is a secretory peptide that inhibits the neurotoxicity of Aβ. However, the mechanism(s) by which HN exerts its neuroprotection against Aβ-induced ADlike pathological changes and memory deficits are yet to be completely defined. In the present study, we provided evidence that treatment of rats with HN increases the number of dendritic branches and the density of dendritic spines, and upregulates pre-and post-synaptic protein levels; these effects lead to enhanced long-term potentiation and amelioration of the memory deficits induced by Aβ 1-42 . HN also attenuated Aβ 1-42 -induced tau hyperphosphorylation, apparently by inhibiting the phosphorylation of Tyr307 on the inhibitory protein phosphatase-2A (PP2A) catalytic subunit and thereby activating PP2A. HN also inhibited apoptosis and reduced the oxidative stress induced by Aβ 1-42 . These fi ndings provide novel mechanisms of action for the ability of HN to protect against Aβ 1-42 -induced AD-like pathological changes and memory defi cits.

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Interaction between the Alzheimer's survival peptide humanin and insulin-like growth factor-binding protein 3 regulates cell survival and apoptosis

Cited by 253 publications

References 31 publications

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

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

Antiangiogenic antitumor activities of IGFBP-3 are mediated by IGF-independent suppression of Erk1/2 activation and Egr-1–mediated transcriptional events

Humanin attenuates Alzheimer-like cognitive deficits and pathological changes induced by amyloid β-peptide in rats

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