The protective effort of GPCR kinase 2–interacting protein‐1 in neurons via promoting Beclin1‐Parkin induced mitophagy at the early stage of spinal cord ischemia‐reperfusion injury

Huang, Yifan; Gu, Changjiang; Qian, Wang; Xu, Lin; Chen, Jian; Zhou, Wei; Zhou, Zheng; Zhao, Shujie; Li, Linwei; Kong, Fanqi; Qian, Dingfei; Zhao, Xuan; Fan, Jin; Li, Qingqing; Yin, Guoyong

doi:10.1096/fj.201902047r

Cited by 21 publications

(7 citation statements)

References 54 publications

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“…As a scaffold protein, GIT1 contains multiple functional regions [ 27 , 28 ]. The GIT1 protein can regulate the level of mitochondrial autophagy during neuronal ischemia-reperfusion by regulating the phosphorylation of Beclin-1 to protect neurons during spinal cord ischemia-reperfusion [ 29 ]. Previous studies have shown that the GIT1 protein can activate Nrf2 of lipopolysaccharide- (LPS-) treated macrophages by regulating the phosphorylation of ERK, thereby reducing the expression of IL-1 β [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

GIT1 Promotes Axonal Growth in an Inflammatory Environment by Promoting the Phosphorylation of MAP1B

Wang

Gao

Líu

et al. 2022

Oxidative Medicine and Cellular Longevity

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Spinal cord injury (SCI) is a severe traumatic condition. The loss of the bundle of axons involved in motor conduction in the spinal cord after SCI is the main cause of motor function injury. Presently, axon regeneration in the spinal cord has been studied extensively, but it remains unclear how axon growth is regulated in an inflammatory environment at the cellular level. In the present study, GIT1 knockout (KO) mouse neurons were cultured in a microfluidic device to simulate the growth of axons in an inflammatory environment. The molecular regulation of axon growth in an inflammatory environment by GIT1 was then investigated. We found that the axon growth of GIT1 KO mouse neurons was restricted in an inflammatory environment. Further investigations revealed that in both axons and cell bodies in the inflammatory environment, GIT1 phosphorylated ERK, promoted the entry of Nrf2 into the nucleus, and promoted the transcription of MAP1B, thereby increasing the levels of MAP1B and p-MAP1B and promoting axon growth. We also found that MAP1B could be translated locally in axons and transported in cell bodies and axons. In conclusion, we found that GIT1 regulated axon growth in an inflammatory environment. This provided a theoretical basis for axon regeneration in an inflammatory environment after SCI to develop new treatment options for axon regeneration.

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Section: Discussionmentioning

confidence: 99%

GIT1 Promotes Axonal Growth in an Inflammatory Environment by Promoting the Phosphorylation of MAP1B

Wang

Gao

Líu

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…It has also been reported that death-associated protein kinase-1 (DAPK1) could phosphorylate the BH3-domain residue Thr119 of BECN1 and consequently abrogate BECN1-BCL2/BCL-XL interaction, facilitating autophagy initiation upon serum deprivation [ 62 ]. In neurons, other type of terminally differentiated cells, GPCR kinase 2-interacting protein-1 (GIT1) regulated the phosphorylation of Beclin-1 at Thr119, which eventually rescued cells from ischemia–reperfusion injury by promotion of mitophagy and inhibition of apoptosis [ 63 ]. Thus, we suggest that heparanase may involve one of the previous regulators, which initiate autophagy and reduce apoptosis after podocyte injury, warranting further investigation.…”

Section: Discussionmentioning

confidence: 99%

Heparanase Increases Podocyte Survival and Autophagic Flux after Adriamycin-Induced Injury

Suleiman

Said

Saleh

et al. 2022

IJMS

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The kidney glomerular filtration barrier (GFB) is enriched with heparan sulfate (HS) proteoglycans, which contribute to its permselectivity. The endoglycosidase heparanase cleaves HS and hence appears to be involved in the pathogenesis of kidney injury and glomerulonephritis. We have recently reported, nonetheless, that heparanase overexpression preserved glomerular structure and kidney function in an experimental model of Adriamycin-induced nephropathy. To elucidate mechanisms underlying heparanase function in podocytes—key GFB cells, we utilized a human podocyte cell line and transgenic mice overexpressing heparanase. Notably, podocytes overexpressing heparanase (H) demonstrated significantly higher survival rates and viability after exposure to Adriamycin or hydrogen peroxide, compared with mock-infected (V) podocytes. Immunofluorescence staining of kidney cryo-sections and cultured H and V podocytes as well as immunoblotting of proteins extracted from cultured cells, revealed that exposure to toxic injury resulted in a significant increase in autophagic flux in H podocytes, which was reversed by the heparanase inhibitor, Roneparstat (SST0001). Heparanase overexpression was also associated with substantial transcriptional upregulation of autophagy genes BCN1, ATG5, and ATG12, following Adriamycin treatment. Moreover, cleaved caspase-3 was attenuated in H podocytes exposed to Adriamycin, indicating lower apoptotic cell death in H vs. V podocytes. Collectively, these findings suggest that in podocytes, elevated levels of heparanase promote cytoprotection.

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“…The Basso Mouse Scale (BMS) test was adopted to evaluate lower limb function recovery as previously documented, 23 on days 1, 3, 7, 14, 21, 28, and 35 postoperation, which was executed by two colleagues blinded to the design of the experiment. 24 Statistical Analysis SPSS 22.0 software was used for statistical analysis.…”

Section: The Basso Mouse Scale (Bms) Testmentioning

confidence: 99%

Amlodipine Improves Spinal Cord Injury Repair by Inhibiting Motoneuronal Apoptosis Through Autophagy Upregulation

Huang

Ren²,

Gao

et al. 2021

Spine

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Study Design. The effect of amlodipine (AM) on spinal cord injury (SCI) and autophagy was researched by establishing ventral spinal cord cells (VSC4.1) oxygen and glucose deprivation model and SCI mice model. Objective. To determine the neuroprotective effects of AM by upregulating autophagy during SCI repair. Summary of Background Data. AM, an antihypertensive medication, has been shown in several studies to inhibit neuronal apoptosis and exert neuroprotective effects in various central nervous system diseases. However, its effects on SCI are unexplored. Autophagy could inhibit cell apoptosis, which has been shown to promote SCI repair. However, the role of AM in autophagy remains unclear. Methods. We examined the relationship between AM, apoptosis, and autophagy in ventral spinal cord cells and the injured spinal cords of C57BL/6 female mice respectively, following histological, behavioral, microscopic, immunofluorescence, and western blotting analyses. Results. We found that AM could inhibit motor neuronal apoptosis in vitro. Furthermore, AM promoted locomotor recovery by upregulating autophagy and alleviating apoptosis, neuronal loss, and spinal cord damage after SCI. Conclusion. AM inhibited motoneuronal apoptosis by upregulating autophagy to improve SCI recovery.

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The protective effort of GPCR kinase 2–interacting protein‐1 in neurons via promoting Beclin1‐Parkin induced mitophagy at the early stage of spinal cord ischemia‐reperfusion injury

Cited by 21 publications

References 54 publications

GIT1 Promotes Axonal Growth in an Inflammatory Environment by Promoting the Phosphorylation of MAP1B

GIT1 Promotes Axonal Growth in an Inflammatory Environment by Promoting the Phosphorylation of MAP1B

Heparanase Increases Podocyte Survival and Autophagic Flux after Adriamycin-Induced Injury

Amlodipine Improves Spinal Cord Injury Repair by Inhibiting Motoneuronal Apoptosis Through Autophagy Upregulation

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