FGF-2 suppresses neuronal autophagy by regulating the PI3K/Akt pathway in subarachnoid hemorrhage

Wang, Yue; Pan, Xiaofei; Liu, Guodong; Liu, Zhuanghua; Zhang, Can; Chen, Tao; Wang, Yuhai

doi:10.1016/j.brainresbull.2021.05.017

Cited by 12 publications

(8 citation statements)

References 32 publications

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“…The intricate molecular mechanism involved in the etiology and pathology of EBI after induction of SAH continues to defy the understanding of researchers. In recent years, a large number of studies have been performed to study EBI from the perspective of alleviating neuronal apoptosis, neuroinflammation, autophagy, and pyroptosis, yet these methods have not achieved satisfactory longterm prognosis in patients suffering from SAH (Zolnourian et al, 2019;Wei et al, 2020;Wang et al, 2021). Therefore, more efforts are needed to gain insight into the molecular mechanism of EBI after SAH, thereby devising potential strategies for clinical intervention.…”

Section: Discussionmentioning

confidence: 99%

“…Early brain injury (EBI) refers to the direct injury in the whole brain that occurs within 72 h after the induction of SAH and is regarded as the major cause of the dismal prognosis of SAH patients (Rass and Helbok, 2019;Qu et al, 2021). Converging evidence suggested a myriad of pathological mechanisms are involved in the pathology of EBI, including apoptosis, autophagy, and pyroptosis (Liu et al, 2020;Wang et al, 2021). Although efforts have been made to develop many drugs targeting these mechanisms, the prognosis of patients suffering from SAH has not been improved considerably (Daou et al, 2019;Neifert et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

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Astragaloside IV attenuates ferroptosis after subarachnoid hemorrhage via Nrf2/HO-1 signaling pathway

Liu

Zhou

et al. 2022

Front. Pharmacol.

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Subarachnoid hemorrhage (SAH) is a severe type of stroke featuring exceptionally high rate of morbidity and mortality due to the lack of effective management. Ferroptosis can be defined as a novel iron-dependent programmed cell death in contrast to classical apoptosis and necrosis. Astragaloside IV (AS-IV) is an active ingredient extracted from Astragalus membranaceus with established therapeutic effect on CNS diseases. However, the exact role of ferroptosis in Astragaloside IV-mediated neuroprotection after SAH is yet to be demonstrated. In the present study, the SAH model of SD male rats with endovascular perforation was used to gauge the neuroprotective effect of AS-IV on SAH-induced early brain injury (EBI) and to clarify the potential molecular mechanism. We found that the induction of SAH reduced the levels of SLC7A11 and glutathione peroxidase 4 (GPX4) in the brain, exacerbated iron accumulation, enhanced lipid reactive oxygen species (ROS) level, and stimulated neuronal ferroptosis. However, the administration of AS-IV and the ferroptosis inhibitor Ferrostatin-1 (Fer-1) enhanced the antioxidant capacity after SAH and suppressed the accumulation of lipid peroxides. Meanwhile, AS-IV triggered Nrf2/HO-1 signaling pathway and alleviated ferroptosis due to the induction of SAH. The Nrf2 inhibitor ML385 blocked the beneficial effects of neuroprotection. These results consistently suggest that ferroptosis is profoundly implicated in facilitating EBI in SAH, and that AS-IV thwarts the process of ferroptosis in SAH by activating Nrf2/HO-1 pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Astragaloside IV attenuates ferroptosis after subarachnoid hemorrhage via Nrf2/HO-1 signaling pathway

Liu

Zhou

et al. 2022

Front. Pharmacol.

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“…This negative correlation was particularly pronounced in patients with favorable outcome, but negligible in the unfavorable group. FGF-2 suppresses autophagy levels; hence, it may reduce post-SAH neuronal apoptosis, providing a neuroprotective role, at least partially, by activating the PI3K/Akt pathway [ 12 , 42 ]. Recently, triggering by receptor expressed on myeloid cell 2 (TREM2) was identified as regulator of both IP-10 and FGF-2 beside others.…”

Section: Discussionmentioning

confidence: 99%

“…To have a broader view of possible pathophysiological processes, we performed a multiplex serum biomarker analysis. The biomarkers measured in this study were selected according to the following criteria: (i) previously their role was investigated in animal models of ischemic stroke or SAH, such as eotaxin [ 11 ], fibroblast growth factor-2 (FGF-2) [ 12 , 13 ], chemokine (C-X3-C motif) ligand-1 (CX3CL1) [ 14 ], or interleukin-1b (Il-1b) [ 15 ]; (ii) its role in the case of SAH has already been investigated, but the studies mainly focused on its level in the CSF, such as monocyte chemotactic protein-3 (MCP-3) [ 10 ]; or (iii) its pathophysiological role was primarily investigated in human ischemic stroke such as Fms related receptor tyrosine kinase-3 ligand (FLT-3L) [ 16 ] and in SAH (interferon gamma-induced protein 10, IP-10) [ 17 , 18 ], macrophage inflammatory protein 1-beta (MIP-1b) [ 17 ], and, further, a more detailed investigation may be promising in the case of SAH. The great variability of temporal patterns of inflammation-related proteins is an indicator of the complexity of the inflammatory response following aSAH.…”

Section: Introductionmentioning

confidence: 99%

Biomarker Associations in Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage

Spantler

Molnár

Simon

et al. 2022

IJMS

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The prognosis for patients with aneurysmal subarachnoid hemorrhage (aSAH) is heavily influenced by the development of delayed cerebral ischemia (DCI), but the adequate and effective therapy of DCI to this day has not been resolved. Multiplex serum biomarker studies may help to understand the pathophysiological processes underlying DCI. Samples were collected from patients with aSAH at two time points: (1) 24 h (Day 1) and (2) 5–7 days after ictus. Serum concentrations of eotaxin, FGF-2, FLT-3L, CX3CL1, Il-1b, IL-4, IP-10, MCP3, and MIP-1b were determined using a customized MILLIPLEX Human Cytokine/Chemokine/Growth Factor Panel A multiplex assay. The functional outcome was defined by the modified Rankin scale (favorable: 0–2, unfavorable: 3–6) measured on the 30th day after aSAH. One-hundred and twelve patients with aSAH were included in this study. The median level of CX3CL1 and MCP-3 measured on Days 5–7 were significantly higher in patients with DCI compared with those without DCI (CX3CL1: with DCI: 110.5 pg/mL, IQR: 82–201 vs. without DCI: 82.6, 58–119, p = 0.036; and MCP-3: with DCI: 22 pg/mL (0–32) vs. without DCI: 0 (0–11), p < 0.001). IP-10, MCP-3, and MIP-1b also showed significant associations with the functional outcome after aSAH. MCP-3 and CX3CL1 may play a role in the pathophysiology of DCI.

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“…Autophagy is a conserved catabolic process that plays a vital role in the regulation of cellular homeostasis. The effect of autophagy could be either destructive or protective for the host ( 7 ). In general, cells deliver the aggregated proteins and damaged organelles into lysosomes to generate metabolites via autophagy ( 8 , 9 ).…”

Section: Introductionmentioning

confidence: 99%

FGF2 Is Protective Towards Cisplatin-Induced KGN Cell Toxicity by Promoting FTO Expression and Autophagy

Wang

et al. 2022

Front. Endocrinol.

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It is widely known that chemotherapy-induced apoptosis of granulosa was the main reason for premature ovarian failure (POF). In addition, accumulating evidence has demonstrated that autophagy was involved in it. Studies before have reported that fibroblast growth factor-2 (FGF2) could attenuate cell death via regulating autophagy. In our previous study, FGF2 could decrease granulosa cell apoptosis in cisplatin-induced POF mice. Furthermore, obesity-associated protein [fat mass and obesity-associated protein (FTO)], which decreased significantly in POF mice, could inhibit cell apoptosis via activating autophagy. Moreover, downregulation of FTO could decrease the expression of paracrine factor FGF2. However, the relationship between FTO and FGF2 in granulosa cell autophagy is still unknown. In the present study, Cell Counting Kit-8 (CCK-8) and 5‐ethynyl‐2‐deoxyuridine (EdU) assays showed that exogenous addition of FGF2 could promote cisplatin-induced injured granulosa cell proliferation. Western blotting indicated that FGF2 could inhibit apoptosis of injured granulosa cells via autophagy. Inhibition of autophagy by chemicals suppressed the effect of FGF2 and promoted injured cell apoptosis. In addition, the expression of FTO was decreased in injured cells, and FGF2 addition could reverse it. Overexpression of FTO reduced injured cell apoptosis via activating the autophagy process. Our findings indicated that FGF2 activates autophagy by regulating the expression of FTO, thereby reducing the apoptosis of the injured cells.

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FGF-2 suppresses neuronal autophagy by regulating the PI3K/Akt pathway in subarachnoid hemorrhage

Cited by 12 publications

References 32 publications

Astragaloside IV attenuates ferroptosis after subarachnoid hemorrhage via Nrf2/HO-1 signaling pathway

Astragaloside IV attenuates ferroptosis after subarachnoid hemorrhage via Nrf2/HO-1 signaling pathway

Biomarker Associations in Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage

FGF2 Is Protective Towards Cisplatin-Induced KGN Cell Toxicity by Promoting FTO Expression and Autophagy

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