Biology subjects

Kakeya, H.

Publications and source records attributed to Kakeya, H..

3 recordsLinked to original sources

bioRxiv2026

Antiglycation effects of imidazole dipeptides and 2-oxo-imidazole dipeptides on glyceraldehyde-induced intracellular protein glycation and neuronal cell death

Glyceraldehyde (GA) contributes to the development of various diseases, such as diabetes and Alzheimers disease via protein glycation and the formation of advanced glycation end products (AGEs); however, effective strategies for neutralizing GA are limited. Carnosine (Car), an imidazole dipeptide (IDP) that is abundant in meat, suppresses protein glycation by scavenging reactive aldehydes. There are only a few reports on the antiglycation activity of Car against GA. For other IDPs, such as anserine, balenine (Bal), and homocarnosine, there are almost no reports on their antiglycation activity. In this study, we demonstrated the antiglycation activity of four types of IDPs and 2-oxocarnosine (2-oxo-Car), an oxidized form of Car, against GA-induced intracellular protein glycation and neuronal cytotoxicity. Car and Bal exhibited significantly higher reactivity with GA compared with other IDPs and 2-oxo-Car. An in silico analysis suggested that the difference in reactivity is dependent upon intramolecular hydrogen bond formation and the conformation of each IDP. Although there were differences in reactivity with GA, LC-MS analysis revealed that all of the IDPs and 2-oxo-Car reacted with two molecules of GA to form adducts containing pyridinium rings. Car and Bal exhibited high reactivity with GA and markedly suppressed GA-induced cytotoxicity in SH-SY5Y cells. Western blot and qPCR analyses revealed that IDPs suppressed GA-induced protein glycation and the upregulation of endoplasmic reticulum and oxidative stress response genes. Our results indicate that IDPs represent a novel preventive approach to AGE-related diseases and provide a foundation for the development of strategies to treat GA-related neurotoxicity. Graphical abstractCarnosine and balenine, which are imidazole dipeptides (IDPs), scavenged two molecules of glyceraldehyde to form adducts containing pyridinium rings and suppressed intracellular protein glycation and neuronal cell death. The formation of intramolecular hydrogen bond of IDPs played a crucial role in the strength of antiglycation activity. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/734660v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@11d82dorg.highwire.dtl.DTLVardef@187aff0org.highwire.dtl.DTLVardef@12fe482org.highwire.dtl.DTLVardef@14327ee_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2026

Ectopic overproduction of cell wall glucan through membrane perturbation by an antifungal peptide theonellamide A in fission yeast

Ergosterol has multiple functions in filamentous fungi and yeasts, although only a part of the functions seems to be understood. An antifungal peptide, theonellamide A (TNM-A) induces drastic morphological changes in fission yeast cells by targeting plasma membrane ergosterol. TNM-A induces overproduction and ectopic accumulation of cell wall glucan at both growing tips and septum through a yet unknown mechanism. Here we show that TNM-A treatment causes accumulation of 1,3-{beta}-glucan at cell-polarity sites, not by increased activity of 1,3-{beta}-glucan synthase, but by an increased, persistent localization of the glucan synthase enzymes. Screening based on subcellular localization of proteins at periphery or polarity sites suggested the involvement of the Rho family GTPase Cdc42. In agreement, TNM-A induced both activation of Cdc42 and enhancement of membrane trafficking of glucan synthase enzymes. In conclusion, our chemical genetics analyses using TNM-A suggest that membrane ergosterol regulates the activity of Cdc42, which further regulates the localization of glucan synthases and cell wall biosynthesis. Highlights (four sentences)- Thenoellamide A (TNM-A) induces an ectopic overproduction of cell wall glucan. - TNM-A treatment causes increased, persistent localization of glucan synthases at the cell tips and septum. - TNM-A activates Cdc42 and upregulates membrane trafficking of glucan synthases. - Ergosterol is involved in proper activation/inactivation of Cdc42.

cell biology↗

bioRxiv2024

Formation of giant ER sheets by pentadecanoic acid causes lipotoxicity in fission yeast

Excess amounts of saturated fatty acids are toxic to organisms, a condition termed lipotoxicity, which is often accompanied by pleiotropic cellular and tissue dysfunction. Here we show that pentadecanoic acid (C15:0) exerts toxicity on the fission yeast Schizosaccharomyces pombe by generating an aberrantly planar endoplasmic reticulum (ER) structure, which we named a "giant ER sheet." Untargeted lipidomics revealed that C15:0 is incorporated into complex lipids depending on an acyl-CoA ligase Lcf1 and an acyl-CoA transferase Slc1, thereby increasing the saturation level of the acyl chains. The toxicity and giant ER sheet formation were abolished by deleting Lcf1 or Slc1, indicating that the incorporation of C15:0 into glycerophospholipids causes giant ER sheet formation. The giant ER sheets disrupted the correct migration of Mid1, a protein determining the cell division site, and physically blocked septum formation, hindering correct cell separation. Our results suggest that the ER is the primary site targeted by saturated fatty acids, leading to lipotoxicity.

cell biology↗