Humanin rescues cultured rat cortical neurons from NMDA-induced toxicity through the alleviation of mitochondrial dysfunction

Cui, Ailing; Zhang, Yinghua; Li, Jianzhong; Song, Tianbin; Liu, Xuemin; Wang, Hui; Zhang, Ce; Ma, Guolin; Zhang, Hui; Li, Kefeng

doi:10.2147/dddt.s133042

Cited by 24 publications

(23 citation statements)

References 36 publications

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“…Similar findings have been seen with adult models of stroke and amyotrophic lateral sclerosis (Matsuoka, Hashimoto, Aiso, & Nishimoto, ; Xu, Chua, Gao, Hamdy, & Chua, ). HN's protective properties have also been demonstrated in cell culture using models of hypoxia, toxins, and conditions of oxidative stress (Cui et al, ; Men, Zhang, Yang, & Gao, ; Sreekumar et al, ; Zhao, Wang, Li, Zhao, & Zhang, ). A common theme in these studies is the promotion of cell survival under stressful conditions such as energy deficit and cellular degeneration/apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Murine maternal dietary restriction affects neural Humanin expression and cellular profile

Baldauf

Sondhi

Shin

et al. 2019

J of Neuroscience Research

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To understand the cellular basis for the neurodevelopmental effects of intrauterine growth restriction (IUGR), we examined the global and regional expression of various cell types within murine (Mus musculus) fetal brain. Our model employed maternal calorie restriction to 50% daily food intake from gestation day 10–19, producing IUGR offspring. Offspring had smaller head sizes with larger head:body ratios indicating a head sparing IUGR effect. IUGR fetuses at embryonic day 19 (E19) had reduced nestin (progenitors), β‐III tubulin (immature neurons), Glial fibrillary acidic protein (astrocytes), and O4 (oligodendrocytes) cell lineages via immunofluorescence quantification and a 30% reduction in cortical thickness. No difference was found in Bcl‐2 or Bax (apoptosis) between controls and IUGR, though qualitatively, immunoreactivity of doublecortin (migration) and Ki67 (proliferation) was decreased. In the interest of examining a potential therapeutic peptide, we next investigated a novel pro‐survival peptide, mouse Humanin (mHN). Ontogeny examination revealed highest mHN expression at E19, diminishing by postnatal day 15 (P15), and nearly absent in adult (3 months). Subanalysis by sex at E19 yielded higher mHN expression among males during fetal life, without significant difference between sexes postnatally. Furthermore, female IUGR mice at E19 had a greater increase in cortical mHN versus the male fetus over their respective controls. We conclude that maternal dietary restriction‐associated IUGR interferes with neural progenitors differentiating into the various cellular components populating the cerebral cortex, and reduces cerebral cortical size. mHN expression is developmental stage and sex specific, with IUGR, particularly in the females, adaptively increasing its expression toward mediating a pro‐survival approach against nutritional adversity.

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Section: Introductionmentioning

confidence: 99%

Murine maternal dietary restriction affects neural Humanin expression and cellular profile

Baldauf

Sondhi

Shin

et al. 2019

J of Neuroscience Research

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“…It is well established that reactive oxygen species (ROS), which are mainly generated in the mitochondrial respiratory chain, impair sperm production, motility, membrane, and DNA integrity and also influence sperm capacitation (Christova et al ., ; Henkel et al ., ; Brouwers et al ., ; Aitken et al ., ; Lee et al ., ). Humanin has been reported to prevent ROS accumulating in cardiomyocytes (Blasco et al ., ), cortical neurons (Cui et al ., ), retinal pigment epithelium (Minasyan et al ., ), and rat pancreatic beta cells (Paharkova et al ., ), etc. Pre‐treatment with humanin analog can exert cardiologically protective effects against myocardial ischemia and reperfusion injury in mouse models (Muzumdar et al ., ).…”

Section: Discussionmentioning

confidence: 99%

Humanin levels in human seminal plasma and spermatozoa are related to sperm quality

Rao

Wen

et al. 2019

Andrology

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Background: Humanin has reportedly been expressed in testis and spermatozoa, but no study has yet reported its presence in human seminal plasma (SP). Objective: The aim of this study was to investigate the presence of humanin in human SP and to determine the correlation between humanin levels in SP/spermatozoa and sperm quality. Materials and methods: Semen samples for SP/sperm humanin level measurement were collected from 164 patients who attended our andrology clinic for fertility evaluation. The localization of humanin in spermatozoa was evaluated using an immunofluorescence method, and SP/sperm humanin levels were measured with ELISA. Correlations between SP/sperm humanin levels and sperm parameters were analyzed. Results: Humanin was expressed in the midpiece of the spermatozoa. Humanin concentrations in the SP ranged from 24.4 to 285.1 pg/mL, with a median of 89.7 pg/mL. The SP humanin concentrations in patients with normospermia were significantly higher than those in patients with oligospermia (p < 0.001), asthenospermia (p = 0.002), and oligoasthenospermia (p < 0.001). Spearman analysis showed a positive and significant correlation between SP humanin concentration and sperm concentration (r = 0.75, p < 0.001), and progressive sperm motility (r = 0.29, p < 0.001). Sperm humanin level was significantly and positively associated with progressive sperm motility (r = 0.70, p < 0.001). In addition, a significantly higher level of humanin was found in swim-up spermatozoa than in non-swim-up spermatozoa (p = 0.03). Conclusions: Seminal plasma and sperm humanin levels were significantly and positively correlated with sperm quality, especially sperm motility. Further studies of the origin of SP humanin and its role in spermatogenesis should be conducted.

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“…These suggest that the mechanism of HN neuroprotection in rat cortical neuron maybe through antagonism of the NMDA receptor. Nonetheless, there is also a conflicting report showing that HN failed to inhibit intracellular Ca 2+ overload triggered by NMDA [ 23 , 30 ]. The reason for the discrepancy is unclear, but one possibility could be due to different concentrations of HN used between these two studies.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, evidence has revealed that HN has a broader spectrum of neuroprotective activity [ 21 , 22 ]. For example, HN has been shown to rescue neurons from NMDA-induced toxicity [ 23 , 24 ]. However, it remains sketchy that the neuroprotection of HN is mediated by the MAPK signals.…”

Section: Introductionmentioning

confidence: 99%

Humanin Attenuates NMDA-Induced Excitotoxicity by Inhibiting ROS-dependent JNK/p38 MAPK Pathway

Yang

Zhang

et al. 2018

IJMS

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Humanin (HN) is a novel 24-amino acid peptide that protects neurons against N-methyl-d-aspartate (NMDA)-induced toxicity. However, the contribution of the different mitogen-activated protein kinases (MAPKs) signals to HN neuroprotection against NMDA neurotoxicity remains unclear. The present study was therefore aimed to investigate neuroprotective mechanisms of HN. We analyzed intracellular Ca2+ levels, reactive oxygen species (ROS) production, and the MAPKs signal transduction cascade using an in vitro NMDA-mediated excitotoxicity of cortical neurons model. Results showed that: (1) HN attenuated NMDA-induced neuronal insults by increasing cell viability, decreasing lactate dehydrogenase (LDH) release, and increasing cell survival; (2) HN reversed NMDA-induced increase in intracellular calcium; (3) pretreatment by HN or 1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid (BAPTA-AM), an intracellular calcium chelator, decreased ROS generation after NMDA exposure; (4) administration of HN or N-Acetyl-l-cysteine (NAC), a ROS scavenger, inhibited NMDA-induced JNK and p38 MAPK activation. These results indicated that HN reduced intracellular elevation of Ca2+ levels, which, in turn, inhibited ROS generation and subsequent JNK and p38 MAPK activation that are involved in promoting cell survival in NMDA-induced excitotoxicity. Therefore, the present study suggests that inhibition of ROS-dependent JNK/p38 MAPK signaling pathway serves an effective strategy for HN neuroprotection against certain neurological diseases.

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Humanin rescues cultured rat cortical neurons from NMDA-induced toxicity through the alleviation of mitochondrial dysfunction

Cited by 24 publications

References 36 publications

Murine maternal dietary restriction affects neural Humanin expression and cellular profile

Murine maternal dietary restriction affects neural Humanin expression and cellular profile

Humanin levels in human seminal plasma and spermatozoa are related to sperm quality

Humanin Attenuates NMDA-Induced Excitotoxicity by Inhibiting ROS-dependent JNK/p38 MAPK Pathway

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