The effects of the heme precursor 5‐aminolevulinic acid (ALA) on REV‐ERBα activation

Abstract

HighlightsREV-ERBα has a key role in circadian rhythms and requires heme as its ligand.Heme precursor ALA exhibited increased nuclear heme level and activation of REV-ERBα.ALA inhibited REV-ERBα target genes including an essential component of the circadian oscillator.

Dietary 5-aminolevulinic acid enhances adenosine triphosphate production, ecdysis and immune response in Pacific white shrimp, Litopenaeus vannamei (Boone)

“…Several studies of vertebrates and vertebrate cell lines support the hypothesis that exogenous 5-ALA enhances haem synthesis and activity of haemoproteins: 5-ALA administration (a) increased intracellular haem levels, increasing the activity of cytochrome P450 in vitro (Miura et al, 2015); (b) increased the activity of cytochrome c oxidase of the electron transport chain and raised ATP levels in mouse liver (Ogura et al, 2011); (c) enhanced protein expression of mitochondrial complexes III-V in mouse adipose tissue (Ota et al, 2017); (d) induced REV-ERBα expression (Yamashita et al, 2014);…”

“…Several studies of vertebrates and vertebrate cell lines support the hypothesis that exogenous 5‐ALA enhances haem synthesis and activity of haemoproteins: 5‐ALA administration (a) increased intracellular haem levels, increasing the activity of cytochrome P450 in vitro (Miura et al., ); (b) increased the activity of cytochrome c oxidase of the electron transport chain and raised ATP levels in mouse liver (Ogura et al., ); (c) enhanced protein expression of mitochondrial complexes III–V in mouse adipose tissue (Ota et al., ); (d) induced REV‐ERBα expression (Yamashita et al., ); and (e) induced both protein and mRNA expression of haem oxygenase‐1 (HO‐1) (a rate‐limiting enzyme in haem degradation) (Nishio et al., : Ito et al., ). 5‐aminolevulinic acid was also reported to enhance the immune response in chickens (Sato et al., ) and pigs (Chen et al., ) and improves growth performance in eels (Yasumoto, Miyanari, Yoshimura, Kondo & Takahashi, ) (although there is some disagreement on the effect of 5‐ALA on growth; see below).…”

“…Haem is a prosthetic group that interacts with different apoproteins to form functional haemoproteins (Kumar & Bandyopadhyay, ). Some examples of haemoproteins include catalase and peroxidase, which protect the body against oxidation by hydrogen peroxide (Tsiftsoglou, Tsamadou & Papadopoulou, ); cytochrome P450 family of enzymes, which metabolize drugs and xenobiotics (Gonzalez & Nebert, ; Miura et al., ); respiratory cytochromes of the mitochondrial electron transport chain which is essential for adenosine triphosphate (ATP) production (Möbius et al., ) and REV‐ERBα (Yamashita et al., ) and its insect homologue nuclear receptor E75 (Reinking et al., ), which have roles in circadian rhythms and ecdysis respectively.…”

The Effect of Iron Ion on the Specificity of Photodynamic Therapy with 5-Aminolevulinic Acid

“…Aliquots of the NaOH-treated cell samples were withdrawn and used for protein concentration assay (Quick Start Bradford protein assay, Bio-Rad Laboratories, Inc., CA, USA), whereas the remaining cellular proteins were denatured by addition of three volumes of solvent A {1 M ammonium acetate, 12.5% acetonitrile (v/v)}:solvent B {50 mM ammonium acetate, 80% acetonitrile (v/v)} (1:9 v/v) solution to the NaOH-treated cell samples. The prepared samples were centrifuged at 10,000 × g for 10 min at 4°C and subjected to high-performance liquid chromatography (HPLC) analysis performed as previously described with some modifications [ 16 – 18 ]. In brief, protoporphyrin IX (PpIX) was separated using the HPLC system (Prominence, Shimadzu, Kyoto, Japan) equipped with a reversed-phase C 18 column (CAPCELL PAK, C18, SG300, 5 μm, 4.6 mm × 250 mm, Shiseido Co., Ltd., Tokyo, Japan).…”

“…NucleoSpin RNA II (MACHEREY-NAGEL, Düren, Mannheim, Germany) was used to extract total RNAs from cells and specimens according to the manufacturer’s protocol. Total RNAs (1 μg) were reverse-transcribed to produce first-strand cDNA using the PrimeScript RT reagent Kit with gDNA Eraser (TaKaRa, Shiga, Japan) according to the manufacturer’s protocol [ 8 , 9 , 18 ]. The Thermal Cycler Dice Real Time System (TaKaRa, Shiga, Japan) was used for a two-step reverse transcription polymerase chain reaction.…”