S14G‐humanin alleviates insulin resistance and increases autophagy in neurons of APP/PS1 transgenic mouse

Han, Kun; Jia, Ning; Zhong, Yi; Shang, Xiuli

doi:10.1002/jcb.26452

Cited by 41 publications

(25 citation statements)

References 24 publications

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“…Induction of insulin resistance in cultured hippocampal neurons showed similar results [39]. After regulating insulin signaling in the hippocampus, the learning ability and memory of AD mice improved [40]. These studies indicated that both abnormal glucose metabolism and insulin resistance can influence neurofunction, even without high glucose.…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 57%

Gp91phox (NOX2) in Activated Microglia Exacerbates Neuronal Damage Induced by Oxygen Glucose Deprivation and Hyperglycemia in an in Vitro Model

Zeng¹,

Ren²,

Zhu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Peri-operative cerebral ischemia reperfusion injury is one of the most serious peri-operative complications that can be aggravated in patients with diabetes. A previous study showed that microglia NOX₂ (a NADPH oxidase enzyme) may play an important role in this process. Here, we investigated whether increased microglial derived gp91^phox, also known as NOX2, reduced oxygen glucose deprivation (OGD) after induction of hyperglycemia (HG). Methods: A rat neuronal-microglial in vitro co-culture model was used to determine the effects of gp91^phox knockdown on OGD after HG using six treatment groups: A rat microglia and neuron co-culture model was established and divided into the following six groups: high glucose + scrambled siRNA transfection (HG, n = 5); HG + gp91^phoxsiRNA transfection (HG-gp91siRNA, n = 5); oxygen glucose deprivation + scrambled siRNA transfection (OGD, n = 5); OGD + gp91^phoxsiRNA transfection (OGD-gp91siRNA, n = 5); HG + OGD + scrambled siRNA transfection (HG-OGD, n = 5); and HG + OGD + gp91^phoxsiRNA transfection (HG-OGD-gp91siRNA, n = 5). The neuronal survival rate was measured by the MTT assay, while western blotting was used to determine gp91^phox expression. Microglial derived ROS and neuronal apoptosis rates were analyzed by flow cytometry. Finally, the secretion of cytokines, including IL-6, IL-8, TNF-α, and 8-iso-PGF2α was determined using an ELISA kit. Results: Neuronal survival rates were significantly decreased by HG and OGD, while knockdown of gp91^phox reversed these rates. ROS production and cytokine secretion were also significantly increased by HG and OGD but were significantly inhibited by knockdown of gp91^phoxsiRNA. Conclusion: Knockdown of gp91^phoxsiRNA significantly reduced oxidative stress and the inflammatory response, and alleviated neuronal damage after HG and OGD treatment in a rat neuronal-microglial co-culture model.

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Section: Cellular Physiology and Biochemistrymentioning

confidence: 57%

Gp91phox (NOX2) in Activated Microglia Exacerbates Neuronal Damage Induced by Oxygen Glucose Deprivation and Hyperglycemia in an in Vitro Model

Zeng¹,

Ren²,

Zhu³

et al. 2018

Cell Physiol Biochem

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“…These peptides, which are generally encoded by small, alternative reading frames of the mitochondrial genome, include humanin, multiple small humanin-like peptides (SHLPs) and mitochondrial-derived peptide MOTSc (also known as MTRNR1) 86 . Humanin not only favours proteostasis and has broad cytoprotective effects coupled to the activation of multiple variants of autophagy 87,88 but also may be involved in the regulation of systemic glucose homeostasis 89 . Along similar lines, MOTSc has been attributed a robust role in the preservation of organismal metabolic homeostasis, most likely reflecting its ability to trigger AMP-activated protein kinase (AMPK) activation in the skeletal muscle 90 .…”

Section: Integrated Stress Responsementioning

confidence: 99%

Linking cellular stress responses to systemic homeostasis

Galluzzi

Yamazaki

Kroemer

2018

Nat Rev Mol Cell Biol

401

245

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| Mammalian cells respond to stress by activating mechanisms that support cellular functions and hence maintain microenvironmental and organismal homeostasis. Intracellular responses to stress, their regulation and their pathophysiological implications have been extensively studied. However, little is known about the signals that emanate from stressed cells to enable a coordinated adaptive response across tissues, organs and the whole organism. Considerable evidence has now accumulated indicating that the intracellular mechanisms that are activated in response to different stresses -which include the DNA damage response, the unfolded protein response, mitochondrial stress signalling and autophagy -as well as the mechanisms ensuring the proliferative inactivation or elimination of terminally damaged cells -such as cell senescence and regulated cell death -are all coupled with the generation of signals that elicit microenvironmental and/or systemic responses. These signals, which involve changes in the surface of stressed cells and/or the secretion of soluble factors or microvesicles, generally support systemic homeostasis but can also contribute to maladaptation and disease. *

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“…Gong et al (41) reported that Hn induced chaperone-mediated autophagy as opposed to macroautophagy. However, Han et al (42) found that Hn induced macroautophagy in the nervous system. cataracts are associated with lens epithelial cells and lens fiber cells.…”

Section: Discussionmentioning

confidence: 99%

Cytoprotective role of humanin in lens epithelial cell oxidative stress‑induced injury

et al. 2020

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oxidative stress-induced injury and apoptosis of human lens epithelial cells (Hlecs) are early events in the development of age-related cataracts (arcs). Humanin (Hn) is a mitochondrial-related peptide that serves a cytoprotective role in various cell types and animal models. Following Hn knockdown or overexpression, the level of reactive oxygen species (roS), mitochondrial membrane potential and mitochondrial dna copy number, cell viability, ldH activity and apoptosis of Hlecs under oxidative stress were detected, and apoptosis and autophagy were detected via transmission electron microscopy. The results suggested that Hn may be involved in the response of Hlecs to oxidative stress, and that HN expression was significantly upregulated under oxidative stress conditions. Furthermore, exogenous Hn reduced intracellular roS content and mitochondrial damage, and enhanced mitochondrial biosynthesis; however, this protection was lost in an endogenous Hn knockdown cell model. in addition, to the best of our knowledge, the present study was the first to identify that Hn increased mitochondrial autophagy, which was involved in reducing roS production under oxidative stress. The present study indicated a potential mechanism underlying the anti-oxidative damage and apoptotic effects of Hn under oxidative stress. in conclusion, Hn may be a potential therapeutic target for ARCs as it has a significant cellular protective effect on Hlecs under oxidative stress; therefore, further study is required to investigate its role in the occurrence and development of arcs.

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S14G‐humanin alleviates insulin resistance and increases autophagy in neurons of APP/PS1 transgenic mouse

Cited by 41 publications

References 24 publications

Gp91phox (NOX2) in Activated Microglia Exacerbates Neuronal Damage Induced by Oxygen Glucose Deprivation and Hyperglycemia in an in Vitro Model

Gp91phox (NOX2) in Activated Microglia Exacerbates Neuronal Damage Induced by Oxygen Glucose Deprivation and Hyperglycemia in an in Vitro Model

Linking cellular stress responses to systemic homeostasis

Cytoprotective role of humanin in lens epithelial cell oxidative stress‑induced injury

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