5-Aminolevulinic acid combined with ferrous iron enhances the expression of heme oxygenase-1

Nishio, Yoshiaki; Fujino, Masayuki; Zhao, Mingyi; Ishii, Takuya; Ishizuka, Masahiro; Ito, Hidenori; Takahashi, Kiwamu; Abe, Fuminori; Nakajima, Motowo; Tanaka, Tohru; Taketani, Shigeru; Nagahara, Yukitoshi; Li, Xiaokang

doi:10.1016/j.intimp.2014.02.003

Cited by 55 publications

(57 citation statements)

References 48 publications

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“…We examined the involvement of MAPK cascades leading to the activation of ERK and p38, as 5-ALA has been shown to activate ERK and p38 16 . As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Coproporphyrinogen III is transported to the mitochondria and it undergoes further biosynthesis, being converted to protoporphyrin IX via the intermediate, protoporphyrinogen IX. Iron is inserted into protoporphyrin IX via a ferrochelatase-catalyzed reaction to eventually generate heme 16–18 . Heme oxygenase-1 (HO-1) is a key enzyme for heme metabolism.…”

Section: Introductionmentioning

confidence: 99%

“…HO-1 metabolizes excess heme, which can cause cell toxicity, and protects cells from oxidative stress 19 . Recent studies have reported that 5-ALA induces the upregulation of HO-1 16–18 . In addition, 5-ALA has been implicated in the treatment of inflammatory disease, autoimmune disease and transplantation due to the anti-inflammatory and immunoregulatory actions that are associated with the expression of HO-1 via mitogen-activated protein kinase (MAPK) activation 16–18 .…”

Section: Introductionmentioning

confidence: 99%

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

Takase

Inden

Sekine

et al. 2017

Sci Rep

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PiT-1 (encoded by SLC20A1) and PiT-2 (encoded by SLC20A2) are type-III sodium-dependent phosphate cotransporters (NaPiTs). Recently, SLC20A2 mutations have been found in patients with idiopathic basal ganglia calcification (IBGC), and were predicted to bring about an inability to transport Pi from the extracellular environment. Here we investigated the effect of low Pi loading on the human neuroblastoma SH-SY5Y and the human glioblastoma A172 cell lines. The results show a different sensitivity to low Pi loading and differential regulation of type-III NaPiTs in these cells. We also examined whether 5-aminolevulinic acid (5-ALA) inhibited low Pi loading-induced neurotoxicity in SH-SY5Y cells. Concomitant application of 5-ALA with low Pi loading markedly attenuated low Pi-induced cell death and mitochondrial dysfunction via the induction of HO-1 by p38 MAPK. The findings provide us with novel viewpoints to understand the pathophysiology of IBGC, and give a new insight into the clinical prevention and treatment of IBGC.

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“…We examined the involvement of MAPK cascades leading to the activation of ERK and p38, as 5-ALA has been shown to activate ERK and p38 16 . As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Takase

Inden

Sekine

et al. 2017

Sci Rep

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“…Furthermore, Sierra-Filardi et al [102] demonstrated that HO-1 is important for the anti-inflammatory activities of M2 macrophages. Therefore, we performed an experiment to determine the effect and signal transduction of 5-ALA/SFC in macrophages with a particular focus on the expression of HO-1 [103]. As shown in Fig.…”

Section: Ho-1 Expression By 5-ala/sfc In Macrophagesmentioning

confidence: 99%

5-Aminolevulinic acid regulates the inflammatory response and alloimmune reaction

Fujino

Nishio

Ito

et al. 2016

International Immunopharmacology

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5-Aminolevulinic acid (5-ALA) is a naturally occurring amino acid and precursor of heme and protoporphyrin IX (PpIX). Exogenously administrated 5-ALA increases the accumulation of PpIX in tumor cells specifically due to the compromised metabolism of 5-ALA to heme in mitochondria. PpIX emits red fluorescence by the irradiation of blue light and the formation of reactive oxygen species and singlet oxygen. Thus, performing a photodynamic diagnosis (PDD) and photodynamic therapy (PDT) using 5-ALA have given rise to a new strategy for tumor diagnosis and therapy. In addition to the field of tumor therapy, 5-ALA has been implicated in the treatment of inflammatory disease, autoimmune disease and transplantation due to the anti-inflammation and immunoregulation properties that are elicited with the expression of heme oxygenase (HO)-1, an inducible enzyme that catalyzes the rate-limiting step in the oxidative degradation of heme to free iron, biliverdin and carbon monoxide (CO), in combination with sodium ferrous citrate (SFC), because an inhibitor of HO-1 abolishes the effects of 5-ALA. Furthermore, NF-E2-related factor 2 (Nrf2), mitogen-activated protein kinase (MAPK), and heme are involved in the HO-1 expression. Biliverdin and CO are also known to have anti-apoptotic, anti-inflammatory and immunoregulatory functions. We herein review the current use of 5-ALA in inflammatory diseases, transplantation medicine, and tumor therapy.

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“…In cultured cells, 100 μM of ALA with SFC demonstrated a nearly 10-fold increase in heme 28 . In the present study, ALA was shown to increase expression of PGC1α, the master regulator of mitochondrial biogenesis, and enhanced muscle mitochondria.…”

Section: Discussionmentioning

confidence: 98%

Treatment of sarcopenia and glucose intolerance through mitochondrial activation by 5-aminolevulinic acid

Fujii

Miyashita

Mitsuishi

et al. 2017

Sci Rep

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Recently, sarcopenia has attracted attention as therapeutic target because it constitutes a risk factor for metabolic and cardiovascular diseases. We focused 5-aminolevulinic acid (ALA) which act as electron carriers in the mitochondrial electron transport system. The mice that received ALA for 8 weeks gained muscle strength and endurance, and exhibited increased muscle mass and mitochondrial amount. Administration of ALA to sarcopenia mice aged 100 weeks and chronic kidney disease (CKD) model mice also increased muscle mass and improved physical performance. Metabolome analysis revealed increased branched-chain amino acids (BCAAs) levels in the skeletal muscle of ALA-treated mice. Quantitative PCR analysis revealed decreased expression levels in branched-chain amino acid transaminases (BCATs) that degrade BCAAs and other muscle-degrading factors, and increased levels of mitochondria-activating factors. We also studied in cultured myocytes and obtained compatible results. ALA-treated mice tended to increase body weight, but reduced blood glucose level. These suggested that ALA treatment not only activated muscle mitochondria but also enhanced muscle mass through an increase in BCAAs contents, as to improve muscle strength, endurance and glucose tolerance in mice. In these ways, muscle mitochondrial activation with ALA is suggested to be useful for the treatment of sarcopenia and glucose intolerance.

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5-Aminolevulinic acid combined with ferrous iron enhances the expression of heme oxygenase-1

Cited by 55 publications

References 48 publications

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

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

5-Aminolevulinic acid regulates the inflammatory response and alloimmune reaction

Treatment of sarcopenia and glucose intolerance through mitochondrial activation by 5-aminolevulinic acid

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