Ginkgolide B Maintains Calcium Homeostasis in Hypoxic Hippocampal Neurons by Inhibiting Calcium Influx and Intracellular Calcium Release

Wang, Li; Lei, Qunfang; Zhao, Shuai; Xu, Wenyuan; Dong, Wei; Jihua, Ran; Shi, Qinghai; Fu, JianFeng

doi:10.3389/fncel.2020.627846

Cited by 17 publications

(7 citation statements)

References 42 publications

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“…Even though ER Ca 2+ depletion represents an undisputed factor of neuronal cell injury, the modulation of the STIM1/ORAI1 complex during ischemia is still under scrutiny. For instance, ORAI1 and STIM1 levels are significantly reduced in hypoxic cortical neurons [50], whereas STIM1 expression is elevated in hippocampal neurons exposed to chemically induced hypoxia [51]. We found that STIM1 levels remain unchanged after long-term incubation with Tg or in the absence of glucose, i.e., when ER is depleted and Ca 2+ entry is stimulated.…”

Section: Discussionmentioning

confidence: 60%

Enhanced Ca2+ Entry Sustains the Activation of Akt in Glucose Deprived SH-SY5Y Cells

Kourti

Liaropoulou

Paschou

et al. 2022

IJMS

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The two crucial cellular insults that take place during cerebral ischemia are the loss of oxygen and loss of glucose, which can both activate a cascade of events leading to neuronal death. In addition, the toxic overactivation of neuronal excitatory receptors, leading to Ca2+ overload, may contribute to ischemic neuronal injury. Brain ischemia can be simulated in vitro by oxygen/glucose deprivation, which can be reversible by the re-establishment of physiological conditions. Accordingly, we examined the effects of glucose deprivation on the PI3K/Akt survival signaling pathway and its crosstalk with HIF-1α and Ca2+ homeostasis in SH-SY5Y human neuroblastoma cells. It was found that glucose withdrawal decreased HIF-1α protein levels even in the presence of the ischemia-mimicking CoCl2. On the contrary, and despite neuronal death, we identified a strong activation of the master pro-survival kinase Akt, a finding that was also confirmed by the increased phosphorylation of GSK3, a direct target of p-Akt. Remarkably, the elevated Ca2+ influx recorded was found to promptly trigger the activation of Akt, while a re-addition of glucose resulted in rapid restoration of both Ca2+ entry and p-Akt levels, highlighting the plasticity of neurons to respond to ischemic challenges and the important role of glucose homeostasis for multiple neurological disorders.

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Section: Discussionmentioning

confidence: 60%

Enhanced Ca2+ Entry Sustains the Activation of Akt in Glucose Deprived SH-SY5Y Cells

Kourti

Liaropoulou

Paschou

et al. 2022

IJMS

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“…LTCCs play a central role in calcium overload, and the regulation of LTCC activity is the focus of considerable research efforts. 53 The inhibition of LTCCs leads to a decrease in Ca 2+ entry, which in turn reduces harmful calcium overload, thereby protecting the heart against ischemic injury. Calcium ion blockers are the most common and widely used drugs for the treatment of MI.…”

Section: Discussionmentioning

confidence: 99%

Cardioprotective effects of alantolactone on isoproterenol-induced cardiac injury and cobalt chloride-induced cardiomyocyte injury

Liu

Zheng

et al. 2022

Int J Immunopathol Pharmacol

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Objectives Alantolactone (AL) is a compound extracted from the roots of Inula Racemosa that has shown beneficial effects in cardiovascular disease. However, the cardioprotective mechanism of AL against hypoxic/ischemic (H/I) injury is still unclear. This research aimed to determine AL’s ability to protect the heart against isoproterenol (ISO)-induced MI injury in vivo and cobalt chloride (CoCl2) induced H/I injury in vitro. Methods Electrocardiography (ECG), lactate dehydrogenase (LDH), creatine kinase (CK), and cardiac troponin I (cTnI) assays in addition to histological analysis of the myocardium were used to investigate the effects of AL in vivo. Influences of AL on L-type Ca2+ current (ICa-L) in isolated rat myocytes were observed by the patch-clamp technique. Furthermore, cell viability, apoptosis, oxidative stress injury, mitochondrial membrane potential, and intracellular Ca2+ concentration were examined in vitro. Results The results indicated that AL treatment ameliorated the morphological and ECG changes associated with MI, and decreased levels of LDH, CK, and cTnI. Furthermore, pretreatment with AL elevated antioxidant enzyme activity and suppressed ROS production. AL prevented H/I-induced apoptosis, mitochondria damage, and calcium overload while reducing ICa-L in a concentration and time dependent fashion. The 50% inhibiting concentration (IC50) and maximal inhibitory effect (Emax) of AL were 17.29 μmol/L and 57.73 ± 1.05%, respectively. Conclusion AL attenuated MI-related injury by reducing oxidative stress, apoptosis, calcium overload, and mitochondria damage. These cardioprotective effects may be related to the direct inhibition of ICa-L.

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“…Thus, CAR has the potential to be an effective therapeutic agent for IS. In 2021, Li et al found that injection of Ginkgolide B (GB) , the active ingredient of terpene lactones ( Wang et al, 2020 ), in an animal model of AD reversed the levels of TFR1 and NOCA4 and upregulated the expression of Nrf2 and GPX4 in the brains of SAMP8 mice, which exhibited neuroprotective effects in AD mice ( Hébert et al, 2022 ).…”

Section: Small Molecule Ferroptosis Inhibitorsmentioning

confidence: 99%

Ferroptosis inhibitors: past, present and future

Zhang,

Luo,

Xiang

et al. 2024

Front. Pharmacol.

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Ferroptosis is a non-apoptotic mode of programmed cell death characterized by iron dependence and lipid peroxidation. Since the ferroptosis was proposed, researchers have revealed the mechanisms of its formation and continue to explore effective inhibitors of ferroptosis in disease. Recent studies have shown a correlation between ferroptosis and the pathological mechanisms of neurodegenerative diseases, as well as diseases involving tissue or organ damage. Acting on ferroptosis-related targets may provide new strategies for the treatment of ferroptosis-mediated diseases. This article specifically describes the metabolic pathways of ferroptosis and summarizes the reported mechanisms of action of natural and synthetic small molecule inhibitors of ferroptosis and their efficacy in disease. The paper also describes ferroptosis treatments such as gene therapy, cell therapy, and nanotechnology, and summarises the challenges encountered in the clinical translation of ferroptosis inhibitors. Finally, the relationship between ferroptosis and other modes of cell death is discussed, hopefully paving the way for future drug design and discovery.

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Ginkgolide B Maintains Calcium Homeostasis in Hypoxic Hippocampal Neurons by Inhibiting Calcium Influx and Intracellular Calcium Release

Cited by 17 publications

References 42 publications

Enhanced Ca2+ Entry Sustains the Activation of Akt in Glucose Deprived SH-SY5Y Cells

Enhanced Ca2+ Entry Sustains the Activation of Akt in Glucose Deprived SH-SY5Y Cells

Cardioprotective effects of alantolactone on isoproterenol-induced cardiac injury and cobalt chloride-induced cardiomyocyte injury

Ferroptosis inhibitors: past, present and future

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