Insulin Growth Factor 1 Protects Neural Stem Cells Against Apoptosis Induced by Hypoxia Through Akt/Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase (Akt/MAPK/ERK) Pathway in Hypoxia-Ishchemic Encephalopathy

Zhao, Bing; Zheng, Zebao

doi:10.12659/msm.901055

Cited by 33 publications

(21 citation statements)

References 33 publications

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“…Our analysis confirmed that AKT phosphorylation, which decreased in hypoxic condition, is recovered by GH treatment, while Bcl2 expression increases in response to GH. In addition, we found that although these were not statistically significant, the absolute levels of phosphorylated AKT and Bcl2 expression increased with the IGF-1 treatment, which is consistent with the numerous evidence, indicating that IGF-1 is an activator of the PIK3/AKT signaling pathway as a mechanism to promote cell survival and inhibit apoptosis [ 14 , 20 , 53 , 54 , 55 , 56 , 57 ].…”

Section: Discussionsupporting

confidence: 87%

Neuroprotective Effects of Growth Hormone (GH) and Insulin-Like Growth Factor Type 1 (IGF-1) after Hypoxic-Ischemic Injury in Chicken Cerebellar Cell Cultures

Baltazar-Lara

Ávila-Mendoza

Martínez-Moreno

et al. 2020

IJMS

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It has been reported that growth hormone (GH) and insulin-like growth factor 1 (IGF-1) exert protective and regenerative actions in response to neural damage. It is also known that these peptides are expressed locally in nervous tissues. When the central nervous system (CNS) is exposed to hypoxia-ischemia (HI), both GH and IGF-1 are upregulated in several brain areas. In this study, we explored the neuroprotective effects of GH and IGF-1 administration as well as the involvement of these endogenously expressed hormones in embryonic chicken cerebellar cell cultures exposed to an acute HI injury. To induce neural damage, primary cultures were first incubated under hypoxic-ischemic (<5% O2, 1g/L glucose) conditions for 12 h (HI), and then incubated under normal oxygenation and glucose conditions (HI + Ox) for another 24 h. GH and IGF-1 were added either during or after HI, and their effect upon cell viability, apoptosis, or necrosis was evaluated. In comparison with normal controls (Nx, 100%), a significant decrease of cell viability (54.1 ± 2.1%) and substantial increases in caspase-3 activity (178.6 ± 8.7%) and LDH release (538.7 ± 87.8%) were observed in the HI + Ox group. On the other hand, both GH and IGF-1 treatments after injury (HI + Ox) significantly increased cell viability (77.2 ± 4.3% and 72.3 ± 3.9%, respectively) and decreased both caspase-3 activity (118.2 ± 3.8% and 127.5 ± 6.6%, respectively) and LDH release (180.3 ± 21.8% and 261.6 ± 33.9%, respectively). Incubation under HI + Ox conditions provoked an important increase in the local expression of GH (3.2-fold) and IGF-1 (2.5-fold) mRNAs. However, GH gene silencing with a specific small-interfering RNAs (siRNAs) decreased both GH and IGF-1 mRNA expression (1.7-fold and 0.9-fold, respectively) in the HI + Ox group, indicating that GH regulates IGF-1 expression under these incubation conditions. In addition, GH knockdown significantly reduced cell viability (35.9 ± 2.1%) and substantially increased necrosis, as determined by LDH release (1011 ± 276.6%). In contrast, treatments with GH and IGF-1 stimulated a partial recovery of cell viability (45.2 ± 3.7% and 53.7 ± 3.2%) and significantly diminished the release of LDH (320.1 ± 25.4% and 421.7 ± 62.2%), respectively. Our results show that GH, either exogenously administered and/or locally expressed, can act as a neuroprotective factor in response to hypoxic-ischemic injury, and that this effect may be mediated, at least partially, through IGF-1 expression.

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Section: Discussionsupporting

confidence: 87%

Neuroprotective Effects of Growth Hormone (GH) and Insulin-Like Growth Factor Type 1 (IGF-1) after Hypoxic-Ischemic Injury in Chicken Cerebellar Cell Cultures

Baltazar-Lara

Ávila-Mendoza

Martínez-Moreno

et al. 2020

IJMS

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“…Our results observed that a large number of apoptotic neurons in VD model rats, while SalB prevented apoptosis of hippocampal neurons in CA1 region in VD model rats. It has been shown that IGF-1 increased cell viability while decreasing apoptosis [36]. Our research suggest that SalB inhibited apoptosis of hippocampal neurons in VD model rats maybe through enchancing hippocampal IGF-1 expression.…”

Section: Discussionmentioning

confidence: 50%

Salvianolic Acid B Ameliorates Cognitive Deficits Through IGF-1/Akt Pathway in Rats with Vascular Dementia

Zhang

et al. 2017

Cell Physiol Biochem

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BackgroundAims: Salvianolic acid B (SalB) is a natural polyphenolic compound enriched in Salvia miltiorrhiza Bunge. Our study was designed to explore the role of Sal B on cognitive impairment in vascular dementia (VD) model rats, as well as its possible molecular mechanisms. Methods: Rats were randomly divided into four groups (n = 15 for each group): Control group, Sal B group (normal Sprague Dawley rats treated with Sal B), VD group and VD + Sal B group. The VD group rats were established by permanent bilateral common carotid artery occlusion (BCCAO). Animals in the Control and Sal B group received the same operation without bilateral common carotid arteries occlusion. The animals in Sal B group and VD + Sal B group received Sal B (20 mg/kg) orally once a day for consecutive 6 weeks. We investigated the effects of SalB on BCCAO-induced cognitive deficits rats models via the Morris water maze experiment. To explore the mechanisms of Sal B on cognitive function, we detected the expression of IGF-1, Akt and p-Akt, and the rate of cell apoptosis in CA1 region. Results: Our results observed that hippocampal IGF-1 was decreased in VD model rats, while SalB reversed the alteration of IGF-1 levels. The expression of hippocampal Akt showed no significant difference between control and VD group, however, p-Akt level was significantly decreased in VD group. After 6 weeks of SalB treatment, p-Akt level was significantly increased. A large number of apoptotic neurons were found in VD model rats, while SalB prevented apoptosis of hippocampal neurons in CA1 region in VD model rats. Conclusion: SalB significantly ameliorated cognitive deficits in BCCAO-induced VD model rats. The potential mechanism underlying the protective effects may be mediated through IGF-1/Akt pathway.

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“…PI3K/Akt-GSK3β signaling contributes to neuronal growth, proliferation, and differentiation of NSCs [61]; promotes hippocampal neurogenesis in a mouse model of Alzheimer’s disease [62]; and ameliorates the apoptosis of neuronal cells in a rat model of Parkinson’s disease [63]. ERK1/2 is a key regulator for neural differentiation [64], modulates neurogenesis [65] and neural apoptosis [66], and improves depression-like behaviors [67]. Activation of ERK and Akt pathways protected PC12 cells against oxidative stress [68], and MG53 activated PI3K/Akt-GSK3β and ERK1/2 signaling to elicit cardioprotective functions [15, 22].…”

Section: Discussionmentioning

confidence: 99%

The TRIM protein Mitsugumin 53 enhances survival and therapeutic efficacy of stem cells in murine traumatic brain injury

et al. 2019

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BackgroundTraumatic brain injury (TBI) is a common neurotrauma leading to brain dysfunction and death. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) hold promise in the treatment of TBI. However, their efficacy is modest due to low survival and differentiation under the harsh microenvironment of the injured brain. MG53, a member of TRIM family protein, plays a vital role in cell and tissue damage repair. The present study aims to test whether MG53 preserves hUC-MSCs against oxidative stress and enhances stem cell survival and efficacy in TBI treatment.MethodsIn this study, we performed a series of in vitro and in vivo experiments in hUC-MSCs and mice to define the function of MG53 enhancing survival, neurogenesis, and therapeutic efficacy of stem cells in murine traumatic brain injury.ResultsWe found that recombinant human MG53 (rhMG53) protein protected hUC-MSCs against H2O2-induced oxidative damage and stimulated hUC-MSC proliferation and migration. In a mouse model of contusion-induced TBI, intravenous administration of MG53 protein preserved the survival of transplanted hUC-MSCs, mitigated brain edema, reduced neurological deficits, and relieved anxiety and depressive-like behaviors. Co-treatment of MG53 and hUC-MSCs enhanced neurogenesis by reducing apoptosis and improving PI3K/Akt-GSK3β signaling.ConclusionMG53 enhances the efficacy of hUC-MSCs in the recovery of TBI, indicating that such adjunctive therapy may provide a novel strategy to lessen damage and optimize recovery for brain injury.

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Insulin Growth Factor 1 Protects Neural Stem Cells Against Apoptosis Induced by Hypoxia Through Akt/Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase (Akt/MAPK/ERK) Pathway in Hypoxia-Ishchemic Encephalopathy

Cited by 33 publications

References 33 publications

Neuroprotective Effects of Growth Hormone (GH) and Insulin-Like Growth Factor Type 1 (IGF-1) after Hypoxic-Ischemic Injury in Chicken Cerebellar Cell Cultures

Neuroprotective Effects of Growth Hormone (GH) and Insulin-Like Growth Factor Type 1 (IGF-1) after Hypoxic-Ischemic Injury in Chicken Cerebellar Cell Cultures

Salvianolic Acid B Ameliorates Cognitive Deficits Through IGF-1/Akt Pathway in Rats with Vascular Dementia

The TRIM protein Mitsugumin 53 enhances survival and therapeutic efficacy of stem cells in murine traumatic brain injury

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