Glycine Protects against Hypoxic-Ischemic Brain Injury by Regulating Mitochondria-Mediated Autophagy via the AMPK Pathway

Cai, Chenchen; Zhu, Jianghu; Ye, Li-Xia; Dai, Yongqiang; Fang, Mingchu; Hu, Yingying; Pan, Shulin; Chen, Si; Li, Peijun; Fu, Xiaoqin; Lin, Zhenlang

doi:10.1155/2019/4248529

Cited by 42 publications

(32 citation statements)

References 72 publications

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“…Therefore, a role of AMPK in hypoxic adaptation seems logical. Indeed, there has been increasing evidence of activation of AMPK acting protectively in hypoxia-associated pathologies, e.g., ischemic injury in heart, brain or guts [26][27][28][29]. By decreasing the cellular ATP consumption, the oxygen demand is also lowered; thus, cellular survival is enhanced [30,31].…”

Section: The Role Of Ampk Under Hypoxiamentioning

confidence: 99%

Activation of AMPK under Hypoxia: Many Roads Leading to Rome

Dengler

2020

IJMS

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AMP-activated protein kinase (AMPK) is known as a pivotal cellular energy sensor, mediating the adaptation to low energy levels by deactivating anabolic processes and activating catabolic processes in order to restore the cellular ATP supply when the cellular AMP/ATP ratio is increased. Besides this well-known role, it has also been shown to exert protective effects under hypoxia. While an insufficient supply with oxygen might easily deplete cellular energy levels, i.e., ATP concentration, manifold other mechanisms have been suggested and are heavily disputed regarding the activation of AMPK under hypoxia independently from cellular AMP concentrations. However, an activation of AMPK preceding energy depletion could induce a timely adaptation reaction preventing more serious damage. A connection between AMPK and the master regulator of hypoxic adaptation via gene transcription, hypoxia-inducible factor (HIF), has also been taken into account, orchestrating their concerted protective action. This review will summarize the current knowledge on mechanisms of AMPK activation under hypoxia and its interrelationship with HIF.

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Section: The Role Of Ampk Under Hypoxiamentioning

confidence: 99%

Activation of AMPK under Hypoxia: Many Roads Leading to Rome

Dengler

2020

IJMS

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“…In neuronal death caused by chronic cerebral hypoperfusion, it is also found that inhibiting excessive mitophagy could exert neuroprotective effects (87). Similarly, inhibition of AMPK-mediated mitophagy could reduce the ischemic and hypoxic damage of neurons in ischemic hypoxic encephalopathy (88).…”

Section: Inhibiting Mitophagy Reduced Cerebral Ischemic-reperfusion Imentioning

confidence: 99%

The Role of Mitophagy in Ischemic Stroke

et al. 2020

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Mitochondria are important places for eukaryotes to carry out energy metabolism and participate in the processes of cell differentiation, cell information transmission, and cell apoptosis. Autophagy is a programmed intracellular degradation process. Mitophagy, as a selective autophagy, is an evolutionarily conserved cellular process to eliminate dysfunctional or redundant mitochondria, thereby fine-tuning the number of mitochondria and maintaining energy metabolism. Many stimuli could activate mitophagy to regulate related physiological processes, which could ultimately reduce or aggravate the damage caused by stimulation. Stroke is a common disease that seriously affects the health and lives of people around the world, and ischemic stroke, which is caused by cerebral vascular stenosis or obstruction, accounts for the vast majority of stroke. Abnormal mitophagy is closely related to the occurrence, development and pathological mechanism of ischemic stroke. However, the exact mechanism of mitophagy involved in ischemic stroke has not been fully elucidated. In this review, we discuss the process and signal pathways of mitophagy, the potential role of mitophagy in ischemic stroke and the possible signal transduction pathways. It will help deepen the understanding of mitophagy and provide new ideas for the treatment of ischemic stroke.

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“…It seems that the two gelatins act as positive allosteric regulators to enhance the efficiency of the calcium-active receptor, thereby activating CaSR, maintaining intracellular calcium homeostasis, and protecting mitochondrial function. On the other hand, glycine, the most abundant amino acid of the two gelatins, could protect against brain injury by regulating mitochondria-mediated autophagy ( Cai et al, 2019 ). Lower level of iron, manganese, and zinc have been observed in patients with Alzheimer’s disease ( Basun et al, 1991 ).…”

Section: Discussionmentioning

confidence: 99%

Tortoise Plastron and Deer Antler Gelatin Prevents Against Neuronal Mitochondrial Dysfunction In Vitro: Implication for a Potential Therapy of Alzheimer’s Disease

et al. 2021

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Mitochondrial dysfunction with oxidative damage plays the fundamental roles in the pathogenesis of Alzheimer’s disease. In traditional Chinese medicine (TCM) practice, animal tissue-derived gelatins are often used as nootropic agents to treat cognitive deterioration and senile dementia. Tortoise plastron gelatin (TPG) and deer antler gelatin (DAG) are the two most commonly used gelatins for this purpose. This study sought to examine the effects of the two gelatins in preventing neuronal mitochondria from oxidative damage. PC12 cells, a cell line derived from rat pheochromocytoma, exposed to the neurotoxin Aβ25–35 served as an in vitro model of Alzheimer’s disease. The cells were separately pre-treated with TPG and DAG at various concentrations ranging from 6.26 µg/ml–200 µg/ml, followed by co-incubation with 20 μM Aβ25–35 for different duration. Cell viability, mitochondrial membrane potential (MMP) and ultrastructure, intracellular ATP, reactive oxygen species (ROS) and calcium (Ca2+) level, the expression of mitochondrial dynamic proteins and biomarkers of apoptosis were measured. Pretreatment with TPG and DAG reversed the Aβ-induced reduction of cell viability in a dose-dependent manner. Both TPG and DAG significantly increased MMP and ATP, alleviated the accumulation of damaged mitochondrial fragments, and normalized the aberrant expression of multiple mitochondrial dynamic proteins of the Aβ-exposed cells. Both gelatins also suppressed intracellular ROS overproduction and Ca2+ overload, overexpression of cytochrome c and pro-apoptosis biomarkers induced by the Aβ exposure. These results suggest that TPG and DAG may have the anti-dementia potential by preventing neuronal mitochondria from oxidative damage.

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Glycine Protects against Hypoxic-Ischemic Brain Injury by Regulating Mitochondria-Mediated Autophagy via the AMPK Pathway

Cited by 42 publications

References 72 publications

Activation of AMPK under Hypoxia: Many Roads Leading to Rome

Activation of AMPK under Hypoxia: Many Roads Leading to Rome

The Role of Mitophagy in Ischemic Stroke

Tortoise Plastron and Deer Antler Gelatin Prevents Against Neuronal Mitochondrial Dysfunction In Vitro: Implication for a Potential Therapy of Alzheimer’s Disease

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