Biology subjects

Tajima, K.

Publications and source records attributed to Tajima, K..

4 recordsLinked to original sources

bioRxiv2023

Cell viability is dominated by quantum effects

Quantum tunneling is a phenomenon in which small quantum particles pass through a reaction energy barrier, as if they were passing through a tunnel opened in the barrier. In this study, we analyzed the involvement of the quantum tunneling effect in enzymatic chemical reactions involving hydrolysis in vitro, by monitoring the kinetic isotope effects due to hydrogen isotopes and their temperature dependence as indicators. The results demonstrated that the quantum tunneling effect is involved in deacetylation, DNA cleavage, and protein cleavage reactions. These related reactions were also examined in terms of their effects on cells, which revealed that the quantum effect is even involved in cell survival, including the almost complete inhibition of DNA homologous recombinational repair. One-Sentence SummaryDue to quantum effects in numerous enzymatic reactions mediated by hydrolysis, heavy water significantly impacts biological outcomes in cells.

biophysics↗

bioRxiv2023

Quantum effects on histone deacetylation and cellular transcription

The question of whether physical phenomena at a quantum level significantly impact aspects of macroscopic life has long remained unanswered. Histone modification by acetylation regulates the transcriptional activity of genes, and thereby broadly impacts cellular metabolism. In chemical reactions, the quantum tunneling effect is a phenomenon in which a small quantum particle of the reactant can pass through the potential energy barrier, even if it does not have sufficient energy to overcome the barrier. Here, we demonstrated that quantum effects are involved in the enzymatic reaction of histone deacetylation, by monitoring kinetic isotope effects due to hydrogen isotopes of water molecules and their temperature dependence as indicators. Due to the kinetic isotope effects associated with the quantum effects, the reaction rate balance between histone acetylation and deacetylation in cells was altered with heavy water, which changed epigenetic transcription regulation in the cells. Thus, microscopic quantum mechanisms exist in histone deacetylation, thereby broadly impacting macroscopic life phenomena through epigenetic regulation. TeaserQuantum effects in enzymatic reaction of histone deacetylation latently influence life phenomena through epigenetic regulation.

biophysics↗

bioRxiv2023

Mechanism Underlying the Immune Responses of a Sublingual Vaccine for SARS-CoV-2 with RBD Antigen and Adjuvant, Poly(I:C) or AddaS03, in Non-human Primates

A sublingual vaccine formulated with recombinant SARS-CoV-2 spike protein receptor binding domain (RBD) antigen and Poly(I:C)) adjuvant was assessed for its safety in non-human primates. This Poly(I:C)-adjuvanted sublingual vaccine was safe compared to the AddaS03-adjuvanted vaccine in blood tests and plasma CRP. The safety of the vaccine was also confirmed through quantitative reverse transcription PCR of six genes and ELISA of four cytokines associated with inflammation and related reactions. The Poly(I:C)- or AddaS03-adjuvanted sublingual vaccine produced RBD-specific IgA antibodies in nasal washings, saliva, and plasma. SARS-CoV-2 neutralizing antibodies were detected in plasma, suggesting that adjuvanted-sublingual vaccines protect against SARS-CoV-2 infection. "Yin and Yang"-like unique transcriptional regulation was observed through DNA microarray analyses of white blood cell RNAs from both vaccines, suppressing and enhancing immune responses and up- or downregulating genes associated with these immune responses. Poly(I:C) adjuvanted sublingual vaccination induced atypical up- or downregulation of genes related to immune suppression or tolerance; Treg differentiation; and T-cell exhaustion. Therefore, Poly(I:C) adjuvant is safe and favorable for sublingual vaccination and can induce a balanced "Yin/Yang" -like effect on immune responses.

immunology↗

bioRxiv2019

Loss of a novel striated muscle-enriched mitochondrial protein Coq10a enhances postnatal cardiac hypertrophic growth

Postnatal mammalian cardiomyocytes undergo a major transition from hyperplasia (increases in cell numbers) to hypertrophy (expansion in cell size). This process is accompanied by rapid mitochondrial biogenesis and metabolic switches to meet the demand of increased cardiac output. Although most mitochondrial components express ubiquitously, recent transcriptomic and proteomic analyses have discovered numerous tissue-specific mitochondrial proteins whose physiological functions are largely unknown. Here we report that a highly evolutionarily conserved mitochondrial protein Coq10a is predominantly expressed in mammalian cardiac and skeletal muscles, and is highly up-regulated around birth in a thyroid hormone-dependent manner. Deletion of Coq10a by CRISPR/Cas9 leads to enhanced cardiac growth after birth. Surprisingly, adult Coq10a mutant mice maintain the hypertrophic heart phenotype with increased levels of coenzyme Q (CoQ) per cardiomyocyte, preserved cardiac contractile function and mitochondrial respiration, which contrasts with reported mice and humans with mutations in other Coq family genes. Further RNA-seq analysis and mitochondrial characterization suggest an increase of mitochondrial biogenesis in the Coq10a mutant heart as a possible consequence of Peroxisome proliferator-activated receptor Gamma Coactivator 1-alpha (PGC1) activation, consistent with a recent intriguing report that CoQ may function as a natural ligand and partial agonist of Peroxisome Proliferator-Activated Receptor (PPAR) /{gamma}. Taken together, our study reveals a previously unknown function of a novel striated muscle-enriched mitochondrial protein Coq10a in regulating postnatal heart growth.

developmental biology↗