Neuroprotective effects of amlodipine besylate and benidipine hydrochloride on oxidative stress-injured neural stem cells

Choi, Na Young; Choi, Hojin; Park, Hyun Hee; Lee, Eun Hye; Yu, Hyun Jeung; Lee, Kyu-Yong; Lee, Young‐Joo; Koh, Seong‐Ho

doi:10.1016/j.brainres.2014.01.016

Cited by 20 publications

(14 citation statements)

References 53 publications

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“…Moreover, destruction of mitochondrial membrane causes the degradation of Bcl-2, an inhibitor for cell death, and also leads to the accumulation and oligomer formation of Bax, which mediate cell apoptosis [41,43]. In our experiments, we detected that treatment of NSCs by H 2 O 2 mediated the cleavage of procaspase-8/9/3, the downregulation of Bcl-2, and upregulation of Bax expression levels, suggesting that the abovementioned apoptotic signals also occurred during oxidative stress-induced NSC death, and these data are consistent with previous investigations [20,49,51]. We further demonstrated that preactivation of mGluR4 in NSCs inhibited the cleavage of procaspase-8/9/3and reversed the H 2 O 2 -induced Bcl-2/ Bax expression levels and the antagonist or gene knockdown abrogated the effects of mGluR4, corroborating the concept of the protection of mGluR4 against NSC oxidative injuries.…”

Section: Fig 8 Protective Effect Of Vu0155041 On H 2 O 2 -Inducedsupporting

confidence: 81%

“…To investigate the involvement of these apoptotic molecules in the mGluR4-mediated inhibition of H 2 O 2 -mediated NSC apoptosis, expression levels of antiapoptotic/apoptotic proteins Bcl-2/Bax and the proapoptotic precursor procaspase-8/9/ 3were estimated by western blot analysis. Consistent with the previous reports [4,20,21], H 2 O 2 stimulation decreased procaspase-8/9/3 and Bcl-2 levels, and increased the Bax expression level (Supplementary Fig. S2).…”

Section: Activation Of Mglur4-protected Nscs Against H 2 O 2 -Inducedsupporting

confidence: 81%

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Activation of Type 4 Metabotropic Glutamate Receptor Attenuates Oxidative Stress-Induced Death of Neural Stem Cells with Inhibition of JNK and p38 MAPK Signaling

Zhang

Wang

et al. 2015

Stem Cells and Development

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1Promoting both endogenous and exogenous neural stem cells' (NSCs) survival in the hostile host environments is essential to cell replacement therapy for central nervous system (CNS) disorders. Type 4 metabotropic glutamate receptor (mGluR4), one of the members of mGluRs, has been shown to protect neurons from acute and chronic excitotoxic insults in various brain damages. The present study investigated the preventive effects of mGluR4 on NSC injury induced by oxidative stress. Under challenge with H 2 O 2 , loss of cell viability was observed in cultured rat NSCs, and treatment with selective mGluR4 agonist VU0155041 conferred protective effects against the loss of cellular viability in a concentration-dependent manner, as shown by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Pretreatment of VU0155041 (30 mM) also inhibited the excessive NSC death induced by H 2 O 2 , and group III mGluRs antagonist (RS)-a-methylserine-O-phosphate (MSOP) or gene-targeted knockdown abolished the protective action of mGluR4, indicated by propidium iodide-Hoechst and terminal deoxynucleotidyl transferase-mediated UTP nick end labeling (TUNEL) staining. Western blot assay demonstrated that mGluR4 activation reversed the decreased procaspase-8/9/3and the destructed Bcl-2/Bax expressing balance, and likewise, MSOP and mGluR4 knockdown abrogated the action of mGluR4 activity. Furthermore, inhibition of JNK and p38 mitogen-activated protein kinases (MAPKs) were observed after mGluR4 activation, and as paralleling control, JNK-specific inhibitor SP600125 and p38-specific inhibitor SB203580 significantly rescued the H 2 O 2 -mediated NSC apoptosis and cleavage of procaspase-3. We suggest that activation of mGluR4 prevents oxidative stress-induced NSC death and apoptotic-associated protein activities with involvement of inhibiting the JNK and p38 pathways in cell culture. Our findings may help to develop strategies for enhancing the resided and transplanted NSC survival after oxidative stress insult of CNS.

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Section: Fig 8 Protective Effect Of Vu0155041 On H 2 O 2 -Inducedsupporting

confidence: 81%

Section: Activation Of Mglur4-protected Nscs Against H 2 O 2 -Inducedsupporting

confidence: 81%

Activation of Type 4 Metabotropic Glutamate Receptor Attenuates Oxidative Stress-Induced Death of Neural Stem Cells with Inhibition of JNK and p38 MAPK Signaling

Zhang

Wang

et al. 2015

Stem Cells and Development

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“…Previously, we reported that amlodipine had possible neuroprotective effects on oxidative stress-injured cortical neurons and NSCs 5,6 . In the present study, we focused on the effects of AC on mitochondrial structure and function in OGD-injured NSCs.…”

Section: Discussionmentioning

confidence: 96%

Mitochondria damaged by Oxygen Glucose Deprivation can be Restored through Activation of the PI3K/Akt Pathway and Inhibition of Calcium Influx by Amlodipine Camsylate

Park

Han

Choi

et al. 2019

Sci Rep

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Amlodipine, a L-type calcium channel blocker, has been reported to have a neuroprotective effect in brain ischemia. Mitochondrial calcium overload leads to apoptosis of cells in neurologic diseases. We evaluated the neuroprotective effects of amlodipine camsylate (AC) on neural stem cells (NSCs) injured by oxygen glucose deprivation (OGD) with a focus on mitochondrial structure and function. NSCs were isolated from rodent embryonic brains. Effects of AC on cell viability, proliferation, level of free radicals, and expression of intracellular signaling proteins were assessed in OGD-injured NSCs. We also investigated the effect of AC on mitochondrial structure in NSCs under OGD by transmission electron microscopy. AC increased the viability and proliferation of NSCs. This beneficial effect of AC was achieved by strong protection of mitochondria. AC markedly enhanced the expression of mitochondrial biogenesis-related proteins and mitochondrial anti-apoptosis proteins. Together, our results indicate that AC protects OGD-injured NSCs by protecting mitochondrial structure and function. The results of the present study provide insight into the mechanisms underlying the protective effects of AC on NSCs.

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“…For example, lead may bind to sulfhydryl groups, leading to a reduction in cellular antioxidant capacity through the depletion of the cellular thiol status and inhibition of antioxidant enzymes, inducing oxidative stress (Ercal et al, 2001). Increased oxidative stress is associated with reduced cell viability and cell proliferation in embryonic and adult neural progenitor cells (Sava et al, 2007; Choi et al, 2014). In our study, we found that lead increased JNK and p38 activation in SGZ-aNPCs.…”

Section: Discussionmentioning

confidence: 99%

Lead decreases cell survival, proliferation, and neuronal differentiation of primary cultured adult neural precursor cells through activation of the JNK and p38 MAP kinases

Engstrom

Wang

Xia

2015

Toxicology in Vitro

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Adult hippocampal neurogenesis is the process whereby adult neural precursor cells (aNPCs) in the subgranular zone (SGZ) of the dentate gyrus (DG) generate adult-born, functional neurons in the hippocampus. This process is modulated by various extracellular and intracellular stimuli, and the adult-born neurons have been implicated in hippocampus-dependent learning and memory. However, studies on how neurotoxic agents affect this process and the underlying mechanisms are limited. The goal of this study was to determine whether lead, a heavy metal, directly impairs critical processes in adult neurogenesis and to characterize the underlying signaling pathways using primary cultured SGZ-aNPCs isolated from adult mice. We report here that lead significantly increases apoptosis and inhibits proliferation in SGZ-aNPCs. In addition, lead significantly impairs spontaneous neuronal differentiation and maturation. Furthermore, we found that activation of the c-Jun NH2-terminal kinase (JNK) and p38 mitogen activated protein (MAP) kinase signaling pathways are important for lead cytotoxicity. Our data suggest that lead can directly act on adult neural stem cells and impair critical processes in adult hippocampal neurogenesis, which may contribute to its neurotoxicity and adverse effects on cognition in adults.

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Neuroprotective effects of amlodipine besylate and benidipine hydrochloride on oxidative stress-injured neural stem cells

Cited by 20 publications

References 53 publications

Activation of Type 4 Metabotropic Glutamate Receptor Attenuates Oxidative Stress-Induced Death of Neural Stem Cells with Inhibition of JNK and p38 MAPK Signaling

Activation of Type 4 Metabotropic Glutamate Receptor Attenuates Oxidative Stress-Induced Death of Neural Stem Cells with Inhibition of JNK and p38 MAPK Signaling

Mitochondria damaged by Oxygen Glucose Deprivation can be Restored through Activation of the PI3K/Akt Pathway and Inhibition of Calcium Influx by Amlodipine Camsylate

Lead decreases cell survival, proliferation, and neuronal differentiation of primary cultured adult neural precursor cells through activation of the JNK and p38 MAP kinases

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