Humanin Inhibits Neuronal Cell Death by Interacting with a Cytokine Receptor Complex or Complexes Involving CNTF Receptor α/WSX-1/gp130

Hashimoto, Yuichi; Kurita, Megumi; Aiso, Sadakazu; Nishimoto, Ikuo; Matsuoka, Masao

doi:10.1091/mbc.e09-02-0168

Cited by 167 publications

(193 citation statements)

References 44 publications

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“…Genes and Vectors-A London-type familial AD-linked amyloid ␤ precursor protein (APP), V642I-APP, in the pcDNA3 vector (Invitrogen) was as described (1,31). A human and mouse SH3BP5 cDNAs were PCR-amplified from total RNA of human neuroblastoma SH-SY5Y and neurohybrid F11 cells, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Secreted Humanin binds to cell-surface formyl peptide receptor-like-1 and inhibits A␤-induced death of PC12 neuronal cells (30). Humanin also inhibits AD-related neuronal death via the heterotrimeric Humanin receptor (htHNR) on the cell membrane, which is composed of ciliary neurotrophic factor receptor ␣, WSX-1, and gp130 (31). The loss-of-function of any of the htHNR subunits abolishes Humanin-induced inhibition of ADrelated neuronal death (31,32).…”

Section: Humanin Is a Secreted Bioactive Peptide That Suppresses Cellmentioning

confidence: 99%

“…Humanin also inhibits AD-related neuronal death via the heterotrimeric Humanin receptor (htHNR) on the cell membrane, which is composed of ciliary neurotrophic factor receptor ␣, WSX-1, and gp130 (31). The loss-of-function of any of the htHNR subunits abolishes Humanin-induced inhibition of ADrelated neuronal death (31,32). The binding of Humanin to htHNR results in oligomerization of the receptor subunits and the activation of JAK2 and STAT3 (22,(31)(32)(33), which is thought to alter expression of target genes of Humanin.…”

Section: Humanin Is a Secreted Bioactive Peptide That Suppresses Cellmentioning

confidence: 99%

“…The loss-of-function of any of the htHNR subunits abolishes Humanin-induced inhibition of ADrelated neuronal death (31,32). The binding of Humanin to htHNR results in oligomerization of the receptor subunits and the activation of JAK2 and STAT3 (22,(31)(32)(33), which is thought to alter expression of target genes of Humanin. However, it remains unknown which target genes of Humanin mediates the neuroprotective effect of Humanin.…”

Section: Humanin Is a Secreted Bioactive Peptide That Suppresses Cellmentioning

confidence: 99%

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SH3-binding Protein 5 Mediates the Neuroprotective Effect of the Secreted Bioactive Peptide Humanin by Inhibiting c-Jun NH2-terminal Kinase

Takeshita

Hashimoto

Nawa

et al. 2013

Journal of Biological Chemistry

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Background: Humanin, a secreted bioactive peptide, suppresses a variety of cell toxicities. Results: An intracellular protein SH3BP5, which directly inhibits JNK activity, is identified as an effector of Humanin. Conclusion: SH3BP5 is a physiological inhibitor of JNK and the firstly identified effector of Humanin. Significance: The discovery provides a novel mechanistic insight into the actions of JNK and Humanin.

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Section: Methodsmentioning

confidence: 99%

Section: Humanin Is a Secreted Bioactive Peptide That Suppresses Cellmentioning

confidence: 99%

Section: Humanin Is a Secreted Bioactive Peptide That Suppresses Cellmentioning

confidence: 99%

Section: Humanin Is a Secreted Bioactive Peptide That Suppresses Cellmentioning

confidence: 99%

See 2 more Smart Citations

SH3-binding Protein 5 Mediates the Neuroprotective Effect of the Secreted Bioactive Peptide Humanin by Inhibiting c-Jun NH2-terminal Kinase

Takeshita

Hashimoto

Nawa

et al. 2013

Journal of Biological Chemistry

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“…Combined with the reported studies, the molecular signaling mechanisms of HN-mediated neuroprotection include stimulation of the PI3 kinase/AKt pathway [56] , inhibition of pro-apoptotic Bcl-2 family members [57] , and modulation of the JAK/STAT pathways [58] by binding to a complex or complexes involving ciliary neurotrophic factor receptor, the IL-27receptor WSX-1, and gp130 [59] .…”

Section: Discussionmentioning

confidence: 93%

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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Calmodulin‐like skin protein suppresses the increase in senescence‐associated β‐galactosidase induced by hydrogen peroxide or ultraviolet irradiation in keratinocytes

Yusuke

Miyachi

Nawa

et al. 2019

Cell Biology International

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Calmodulin‐like skin protein (CLSP) is a secreted peptide that is produced by skin keratinocytes and some related epithelial cells. It has previously been shown that CLSP is recruited via the bloodstream into the central nervous system where it likely exerts a neuroprotective effect against toxicity related to Alzheimer's disease (AD) by binding to the heterotrimeric humanin receptor and activating intracellular survival signaling. However, it remains to be elucidated whether secreted CLSP shows a protective effect in the skin tissues. In the current study, using primary keratinocytes treated with hydrogen peroxide (H2O2) or exposed to ultraviolet (UV) irradiation as senescence models of keratinocytes, we addressed whether CLSP affects senescence in skin keratinocytes. We found that CLSP expression was upregulated by H2O2 or UV in keratinocytes. Furthermore, co‐incubation with recombinant CLSP reduced the increase in senescence‐associated β‐galactosidase‐positivity in keratinocytes that were induced by H2O2 or UV. These results suggest that CLSP may function as a senescence‐suppressing factor in keratinocytes.

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Humanin Inhibits Neuronal Cell Death by Interacting with a Cytokine Receptor Complex or Complexes Involving CNTF Receptor α/WSX-1/gp130

Abstract: Humanin (HN) inhibits neuronal death induced by various

Cited by 167 publications

References 44 publications

SH3-binding Protein 5 Mediates the Neuroprotective Effect of the Secreted Bioactive Peptide Humanin by Inhibiting c-Jun NH2-terminal Kinase

SH3-binding Protein 5 Mediates the Neuroprotective Effect of the Secreted Bioactive Peptide Humanin by Inhibiting c-Jun NH2-terminal Kinase

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

Calmodulin‐like skin protein suppresses the increase in senescence‐associated β‐galactosidase induced by hydrogen peroxide or ultraviolet irradiation in keratinocytes

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