Neuroprotective effect of 5-aminolevulinic acid against low inorganic phosphate in neuroblastoma SH-SY5Y cells

Takase, Naoko; Inden, Masatoshi; Sekine, Shin-ichiro; Ishii, Yumi; Yonemitsu, Hiroko; Iwashita, Wakana; Kurita, Hisaka; Taketani, Yutaka

doi:10.1038/s41598-017-06406-6

Cited by 12 publications

(6 citation statements)

References 34 publications

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“…Subsequently, disrupted Pi homeostasis inside and outside cells is expected to occur in IBGC. In our previous study, we demonstrated that mitochondrial-related ROS were produced by the disruption of Pi homeostasis [59]. In the present study, we showed that 12AC3O reduced the signal of Mito SOX, which evaluates mitochondrial oxidative stress.…”

Section: Discussionsupporting

confidence: 57%

The Novel gem-Dihydroperoxide 12AC3O Suppresses High Phosphate-Induced Calcification via Antioxidant Effects in p53LMAco1 Smooth Muscle Cells

Takase

Inden

Hirai

et al. 2020

IJMS

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The excessive intake of phosphate (Pi), or chronic kidney disease (CKD), can cause hyperphosphatemia and eventually lead to ectopic calcification, resulting in cerebrovascular diseases. It has been reported that reactive oxygen species (ROS), induced by high concentrations of Pi loading, play a key role in vascular calcification. Therefore, ROS suppression may be a useful treatment strategy for vascular calcification. 12AC3O is a newly synthesized gem-dihydroperoxide (DHP) that has potent antioxidant effects. In the present study, we investigated whether 12AC3O inhibited vascular calcification via its antioxidative capacity. To examine whether 12AC3O prevents vascular calcification under high Pi conditions, we performed Alizarin red and von Kossa staining, using the mouse aortic smooth muscle cell line p53LMAco1. Additionally, the effect of 12AC3O against oxidative stress, induced by high concentrations of Pi loading, was investigated using redox- sensitive dyes. Further, the direct trapping effect of 12AC3O on reactive oxygen species (ROS) was investigated by ESR analysis. Although high concentrations of Pi loading exacerbated vascular smooth muscle calcification, calcium deposition was suppressed by the treatment of both antioxidants and 12AC3O, suggesting that the suppression of ROS may be a candidate therapeutic approach for treating vascular calcification induced by high concentrations of Pi loading. Importantly, 12AC3O also attenuated oxidative stress. Furthermore, 12AC3O directly trapped superoxide anion and hydroxyl radical. These results suggest that ROS are closely involved in high concentrations of Pi-induced vascular calcification and that 12AC3O inhibits vascular calcification by directly trapping ROS.

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Section: Discussionsupporting

confidence: 57%

The Novel gem-Dihydroperoxide 12AC3O Suppresses High Phosphate-Induced Calcification via Antioxidant Effects in p53LMAco1 Smooth Muscle Cells

Takase

Inden

Hirai

et al. 2020

IJMS

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“…9,10 ALA reportedly exerts a broad range of cytoprotective effects against cisplatin-induced nephrotoxicity, rhabdomyolysis-induced acute kidney injury, hypoxia-induced cardiomyocyte injury, and low phosphorus loading-induced neurotoxicity through its antioxidant abilities. [10][11][12][13] Herein, we investigated the potential use of ALA as a novel radioprotective drug for normal rectal and bladder mucosa.…”

Section: Discussionmentioning

confidence: 99%

“…ALA is distributed ubiquitously in mammalian cells and is a precursor of tetrapyrole compounds such as heme, which is essential in aerobic energy metabolism and the electron transport system . ALA reportedly exerts a broad range of cytoprotective effects against cisplatin‐induced nephrotoxicity, rhabdomyolysis‐induced acute kidney injury, hypoxia‐induced cardiomyocyte injury, and low phosphorus loading‐induced neurotoxicity through its antioxidant abilities . Herein, we investigated the potential use of ALA as a novel radioprotective drug for normal rectal and bladder mucosa.…”

Section: Introductionmentioning

confidence: 99%

Dual benefit of supplementary oral 5‐aminolevulinic acid to pelvic radiotherapy in a syngenic prostate cancer model

et al. 2018

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Background Normal tissue damage caused by radiotherapy remains the largest dose‐limiting factor in radiotherapy for cancer. Therefore, the aim of this study was to investigate the supplementary oral 5‐aminolevulinic acid (ALA) to standard radiation therapy as a novel radioprotective approach that would not compromise the antitumor effect of radiation in normal rectal and bladder mucosa in a syngenic prostate cancer (PCa) model. Methods To evaluate the radiosensitizing effect of ALA in vitro, clonogenic survival assays were performed in DU145, PC3, and MyC‐CaP cell lines. To evaluate the effect of ALA in vivo a single dose (25 Gy) of radiation with or without ALA was given to healthy mice. Next, a syngenic PCa model of MyC‐CaP cells in FVB mice was created, and multiple doses (12 Gy total) of radiation were administered to the mouse pelvic area with or without ALA administration. Resected tumors, recta, and urinary bladders were immunostained with antibodies against Ki‐67, γ‐H2AX, CD204, and uroplakin‐III. Total RNA levels in recta and urinary bladders were analyzed via RT2 Profiler polymerase chain reaction (PCR) arrays related to “Stress & Toxicity PathwayFinder,” “Mitochondria,” and “Inflammasomes.” Results The addition of in vitro single or in vivo repeated administration of exogenous ALA acted as a radiosensitizer for PCa cells. Rectal toxicity was characterized by histological changes including loss of surface epithelium, fibrosis, severe DNA damage, and the aggregation of M2 macrophages. Urinary bladder toxicity was characterized by bladder wall thickening and urothelium denuding. The higher dose (300 mg/kg/day) of ALA exerted a better radioprotective profile than the lower dose (30 mg/kg/day) in normal recta and urinary bladders. Out of the 252 genes tested, 35 (13.4%) were detected as relevant genes which may be involved in the radioprotective role of ALA administration. These included interleukin‐1a (IL‐1a), IL‐1b, IL‐12, chemokine (C‐X‐C motif) ligand 1 (CXCL1), CXCL3, and NLRP3. Conclusions Our study provides novel and comprehensive insights into the dual benefits including radiosensitizing PCa tumor tissues and radioprotection of normal pelvic organs from radiation therapy. Knowledge of the underlying mechanism will facilitate the search for optimal treatment parameters for supplemental oral ALA during radiotherapy for PCa.

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“…However, mitochondrial dysfunction is also downstream of these signaling pathways. In addition, some ion homeostasis and cell metabolism–related proteins were also found to be downregulated in synaptosomes based on our proteomic analysis, such as those in the solute carrier family (SLC9A6, SLC20A2) and potassium voltage‐gated channel subfamily A2 (KCNA2), tubulin alpha 8 (TUBA8), and tubulin beta 2B (TUBB2), all of which are highly associated with mitochondria during cell metabolism or apoptosis (Table S3, Supporting Information) . Therefore, our results reveal that Ginseng can regulate the function of mitochondria and may be useful for the treatment of central nervous diseases.…”

Section: Discussionmentioning

confidence: 62%

Revealing the Inhibitory Effect of Ginseng on Mitochondrial Respiration through Synaptosomal Proteomics

Kong

Tian

et al. 2018

Proteomics

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Ginseng, the active ingredients of which are ginsenosides, is the most popular herbal medicine and has potential merit in the treatment of cerebral disorders. To better understand the function of Ginseng in the cerebral system, we examined changes in the protein expression profiles of synaptosomes extracted from the cerebral cortical and hippocampal tissues of rats administered a high or low dose of Ginseng for 2 weeks. More than 5000 proteins belonging to synaptosomes were simultaneously identified and quantitated by an approach combining tandem mass tags with 2D liquid chromatography-mass spectrometry (LC-MS). Regarding differentially expressed proteins, downregulated proteins were much more highly induced than upregulators in the cerebral cortical and hippocampal synaptosomes, regardless of the dose of Ginseng. Bioinformatic analysis indicated the majority of the altered proteins to be located in the mitochondria, directly or indirectly affecting mitochondrial oxidative respiration. Further functional experiments using the substrate-uncoupler inhibitor titration approach confirmed that three representative ginsenosides were able to inhibit oxidative phosphorylation in mitochondria. Our results demonstrate that Ginseng can regulate the function of mitochondria and alter the energy metabolism of cells, which may be useful for the treatment of central nervous disorders.

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Neuroprotective effect of 5-aminolevulinic acid against low inorganic phosphate in neuroblastoma SH-SY5Y cells

Cited by 12 publications

References 34 publications

The Novel gem-Dihydroperoxide 12AC3O Suppresses High Phosphate-Induced Calcification via Antioxidant Effects in p53LMAco1 Smooth Muscle Cells

The Novel gem-Dihydroperoxide 12AC3O Suppresses High Phosphate-Induced Calcification via Antioxidant Effects in p53LMAco1 Smooth Muscle Cells

Dual benefit of supplementary oral 5‐aminolevulinic acid to pelvic radiotherapy in a syngenic prostate cancer model

Revealing the Inhibitory Effect of Ginseng on Mitochondrial Respiration through Synaptosomal Proteomics

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