Biology subjects

Baba, O.

Publications and source records attributed to Baba, O..

3 recordsLinked to original sources

bioRxiv2026

Gluconeogenesis and glycogen metabolism in the epidermis and endoderm of Xenopus tropicalis embryos and larvae.

In many oviparous animals, egg yolk is the sole source of nutrition until feeding begins, and carbohydrates are present in only small amounts in the yolk. Glucose plays an important role in the developmental processes of various animals. In addition, gluconeogenesis has been reported to occur in the yolk syncytial layer (YSL) of cartilaginous fish and teleosts. In contrast, the role of gluconeogenesis in tetrapods remains unclear. In this study, we used Xenopus tropicalis, an anuran amphibian, which lacks YSL, and therefore provide an opportunity to examine the evolutionary conservation of gluconeogenic mechanisms among vertebrates. In X. tropicalis, liquid chromatography/mass spectrometry revealed that glucose levels increased before liver formation. Subsequent tracer experiments using 13C-labeled metabolic substrates detected gluconeogenesis activity from glycerol and lactate. Expression analyses showed that gluconeogenic genes are expressed in the epidermis and endoderm. Consistently, generation 0 (G0) knockout of fbp1, a key gluconeogenic gene, resulted in a significant reduction in glucose levels, affecting brain development. These findings first demonstrate that gluconeogenesis supports development of X. tropicalis. To the best of our knowledge, gluconeogenesis in developing epidermis has not been reported, highlighting previously unrecognized diversity in tissue-specific metabolism during vertebrate development. Comparative analyses across species will provide further insights into the evolution and functional significance of embryonic gluconeogenesis and nutrient metabolism.

developmental biology↗

bioRxiv2024

A novel VCP modulator, KUS121, attenuates atherosclerosis progression by maintaining intracellular ATP and mitigating ER stress in endothelial cells

BackgroundEndoplasmic reticulum (ER) stress signaling pathways have pivotal roles in atherosclerosis progression. Recently, we have developed Kyoto University Substance (KUS) 121, which selectively inhibits ATPase activities of valosin-containing protein (VCP) and consequently saves intracellular ATP consumption and mitigates ER stress. Methods and ResultsWe assessed the efficacy of KUS121 against atherosclerosis by its daily injection into Apoe-/- mice fed with Western Diet (WD) for 8 weeks. Consequently, KUS121 treatment reduced atherosclerosis progression by approximately 40% in atherosclerotic plaques. Interestingly, we found that C/EBP homologous protein (CHOP), an established ER stress marker, was mainly expressed in plaque endothelium. Therefore, we assessed the action of KUS121 in endothelial cells using the human endothelial cell line (EA.hy926 cells). As a result, KUS121 prevented ER stress-induced apoptosis and downregulated the IRE1 (Inositol-requiring enzyme) -associated inflammatory pathways. Consistent with these in vitro findings, KUS121 treatment also significantly reduced endothelial apoptosis assessed by TUNEL staining and inflammation examined by immunostaining of Nuclear factor kappa B (NF-{kappa}B) and Intercellular adhesion molecule (ICAM) 1 at plaque endothelium. We also demonstrated that KUS121 maintained ATP levels in EA.hy926 cells and atherosclerotic plaque lesions using the single-wavelength or the FRET-based fluorescent ATP sensor. Supplementation of intracellular ATP by Methyl pyruvate (MePyr) attenuated ER stress-induced apoptotic and inflammatory pathways in endothelial cells, which could be the main mechanism how KUS121 reduces ER stress. ConclusionsKUS121 can be a new therapeutic option for atherosclerotic diseases by maintaining intracellular ATP levels and attenuating ER stress-induced apoptosis and inflammation in plaque endothelium.

pathology↗

bioRxiv2020

CXCR4-binding PET tracers link monocyte recruitment and endothelial injury in murine atherosclerosis

Viral macrophage inflammatory protein 2 (vMIP-II/vCCL2) binds to multiple chemokine receptors, and vMIP-II based PET tracer (64Cu-DOTA-vMIP-II: vMIP-II tracer) accumulates at atherosclerotic lesions in mice. The magnitude of 64Cu-DOTA-vMIP-II accumulation correlated with monocyte recruitment, as Apoe-/- mice treated with AAV-mApoE showed PET signal declining as monocyte recruitment subsided. Unexpectedly, monocytes themselves were not the major target of the 64Cu-DOTA-vMIP-II tracer. Using fluorescence-tagged vMIP-II tracer, competitive receptor blocking with CXCR4 antagonists, CXCR4-specific tracer 64Cu-DOTA-FC131, or CXCR4 staining during disease progression and regression, endothelial cell expression of CXCR4 proved to be the main target of 64Cu-DOTA-vMIP-II imaging. Expression of CXCR4 was low in non-plaque areas, but strongly detected on endothelium at the edges of progressing plaques, corresponding to a population of proliferating endothelium and to the location in plaques where monocyte recruitment occurred. Thus, endothelial injury status of plaques is marked by CXCR4 expression and that this injury correlates with the tendency of such plaques to recruit monocytes. Furthermore, our findings suggest PET tracers that, through binding CXCR4, may be useful to monitor plaque injury status.

pathology↗