Central Taurine Attenuates Hyperthermia and Isolation Stress Behaviors Augmented by Corticotropin-Releasing Factor with Modifying Brain Amino Acid Metabolism in Neonatal Chicks

The objective of this study was to determine the effects of centrally administered taurine on rectal temperature, behavioral responses and brain amino acid metabolism under isolation stress and the presence of co-injected corticotropin-releasing factor (CRF). Neonatal chicks were centrally injected with saline, 2.1 pmol of CRF, 2.5 μmol of taurine or both taurine and CRF. The results showed that CRF-induced hyperthermia was attenuated by co-injection with taurine. Taurine, alone or with CRF, significantly decreased the number of distress vocalizations and the time spent in active wakefulness, as well as increased the time spent in the sleeping posture, compared with the saline- and CRF-injected chicks. An amino acid chromatographic analysis revealed that diencephalic leucine, isoleucine, tyrosine, glutamate, asparagine, alanine, β-alanine, cystathionine and 3-methylhistidine were decreased in response to taurine alone or in combination with CRF. Central taurine, alone and when co-administered with CRF, decreased isoleucine, phenylalanine, tyrosine and cysteine, but increased glycine concentrations in the brainstem, compared with saline and CRF groups. The results collectively indicate that central taurine attenuated CRF-induced hyperthermia and stress behaviors in neonatal chicks, and the mechanism likely involves the repartitioning of amino acids to different metabolic pathways. In particular, brain leucine, isoleucine, cysteine, glutamate and glycine may be mobilized to cope with acute stressors.

Metabolomics Study with Gas Chromatography-Mass Spectrometry of Hepatotoxicity on Adult Zebrafish (Brachydanio Rerio) after Exposure to Diquat

Although diquat is a widely used water-soluble herbicide in the world, its toxicity to freshwater fish has not been well characterized. In this study, gas chromatography-mass spectrometry (GC-MS) based metabolomics approach combined with histopathological examination and biochemical assays was applied to comprehensively assess the hepatotoxicity in zebrafish (Brachydanio rerio) after diquat exposure at two dosages of 0.34 and 1.69 mg·L−1 for 35 days. The results indicated that 1.69 mg·L−1 diquat exposure cause serious cellular swell and vacuolization with increased nuclear abnormality, and lead to obvious disturbance of antioxidative system and dysfunction in liver; while no obvious pathological injury could be detected, and changes in liver biochemistry were less pronounced at the dose level of 0.34 mg·L−1. Multivariate statistical analysis and pattern recognition showed different GC-MS profiles of zebrafish liver following exposure to diquat, the cluster of the treated groups were both clearly separated from the control samples. The differentially abundant metabolites mainly include carbohydrates, amino acids, lipids, nucleotides, and their derivatives. In the exposure group of 1.69 mg·L−1 diquat, severe disturbances of amino acid metabolism played important biological roles associated with inhibition of energy metabolism, reduced immunity, and disorders in neurotransmitters as pathway analysis revealed. Additionally, fluctuation of inositol, creatine, and pantothenic acid, substances associated with stress regulation and signal transduction, participating in metabolic abnormalities in zebrafish with diquat-triggered hepatic damage. Energy metabolism of zebrafish exposed on 0.34 mg·L−1 diquat more inclined to rely on anaerobic glycolysis than the normal ones. Amino acid metabolism responses were less affected, but obvious interference effects on lipid metabolism were observed with 0.34 mg·L−1 diquat exposure. These results imply increased sensitivity of metabolomics versus histopathology and clinical chemistry in recognizing liver toxicity of diquat. This study will contribute to explore possible mechanism of hepatic damages on nontarget freshwater fish induced by diquat and provide important basis for its environmental risk assessment.

Red Light Regulates the Metabolite Biosynthesis in the Leaves of “Huangjinya” Through Amino Acid and Phenylpropanoid Metabolisms

“Huangjinya” is a light-sensitive albino variety and is widely cultivated in China. It has been proved that red light could promote the vegetable growth of plants. However, the mechanism of “Huangjinya” in response to a red light is unclear. This study used high-throughput sequencing technology to analyze the transcriptome of tender shoots of “Huangjinya” under the white and red light supplement conditions. At the same time, liquid chromatography tandem mass spectrometry (LC-MS) was used to analyze metabolite changes under different light conditions. Transcriptome analysis revealed that a total of 174 differentially expressed genes (DEGs) were identified after the red light supplement. Kyoto encyclopedia of genes and genomes (KEGG) classification indicated that amino acid metabolism enriched the most DEGs. In addition, two phenylpropanoid metabolism-related genes and five glutathione S-transferase genes (CsGSTs) were found to be expressed differently. Metabolome analysis revealed that 193 differential metabolites were obtained. Being the same as transcriptome analysis, most differential metabolites were enriched in amino acids, sweet and umami tasting amino acids were increased, and bitter-tasting amino acids were decreased after the red light supplement. In summary, red light supplementary treatment may be propitious to the quality of “Huangjinya” due to its regulatory effect on amino acid metabolism. Also, CsGSTs involved phenylpropanoid metabolism contributed to tea quality changes in “Huangjinya.”

Schwann Cells Accelerate Osteogenesis via the Mif/CD74/FOXO1 Signaling Pathway In Vitro

Schwann cells have been found to promote osteogenesis by an unclear molecular mechanism. To better understand how Schwann cells accelerate osteogenesis, RNA-Seq and LC-MS/MS were utilized to explore the transcriptomic and metabolic response of MC3T3-E1 to Schwann cells. Osteogenic differentiation was determined by ALP staining. Lentiviruses were constructed to alter the expression of Mif (macrophage migration inhibitory factor) in Schwann cells. Western blot (WB) analysis was employed to detect the protein expression. The results of this study show that Mif is essential for Schwann cells to promote osteogenesis, and its downstream CD74/FOXO1 is also involved in the promotion of Schwann cells on osteogenesis. Further, Schwann cells regulate amino acid metabolism and lipid metabolism in preosteoblasts. These findings unveil the mechanism for Schwann cells to promote osteogenesis where Mif is a key factor.

Effects of Heat Stress on the Ruminal Epithelial Barrier of Dairy Cows Revealed by Micromorphological Observation and Transcriptomic Analysis

Heat stress (HS) alters the rumen fermentation of dairy cows thereby affecting the metabolism of rumen papillae and thus the epithelial barrier function. The aim of the present study was to investigate if HS damages the barrier function of ruminal epithelia. Eight multiparous Holstein dairy cows with rumen cannula were randomly equally allocated to two replicates (n = 4), with each replicate being subjected to heat stress or thermal neutrality and pair-feeding in four environmental chambers. Micromorphological observation showed HS aggravated the shedding of the corneum and destroyed the physical barrier of the ruminal epithelium to a certain extent. Transcriptomics analysis of the rumen papillae revealed pathways associated with DNA replication and repair and amino acid metabolism were perturbated, the biological processes including sister chromatid segregation, etc. were up-regulated by HS, while the MAPK and NF-kB cell signaling pathways were downregulated. However, no heat stress-specific change in the expression of tight junction protein or TLR4 signaling was found, suggesting that HS negatively affected the physical barrier of the ruminal epithelium to some extent but did not break the ruminal epithelium. Heat stress invoked mechanisms to maintain the integrity of the rumen epithelial barrier by upregulating the expression of heat shock protein and repairments in rumen papillae. The increase in amino acid metabolism in rumen papillae might affect the nutrient utilization of the whole body. The findings of this study may inform future research to better understand how heat stress affects the physiology and productivity of lactating cows and the development of mitigation strategies.

Biosensor for branched-chain amino acid metabolism in yeast and applications in isobutanol and isopentanol production

Branched-chain amino acid (BCAA) metabolism fulfills numerous physiological roles and can be harnessed to produce valuable chemicals. However, the lack of eukaryotic biosensors specific for BCAA-derived products has limited the ability to develop high-throughput screens for strain engineering and metabolic studies. Here, we harness the transcriptional regulator Leu3p from Saccharomyces cerevisiae to develop a genetically encoded biosensor for BCAA metabolism. In one configuration, we use the biosensor to monitor yeast production of isobutanol, an alcohol derived from valine degradation. Small modifications allow us to redeploy Leu3p in another biosensor configuration that monitors production of the leucine-derived alcohol, isopentanol. These biosensor configurations are effective at isolating high-producing strains and identifying enzymes with enhanced activity from screens for branched-chain higher alcohol (BCHA) biosynthesis in mitochondria as well as cytosol. Furthermore, this biosensor has the potential to assist in metabolic studies involving BCAA pathways, and offers a blueprint to develop biosensors for other products derived from BCAA metabolism.

Understanding the relationship between the microbiome and the structure and function of the pig gastrointestinal tract

The gut epithelium acts as a barrier to the gut environment. The integrity of the epithelial structure and function is thus critical for microbiome-host interaction. The gut microbiome can regulate the utilization and synthesis of mucin, the expressions of the intercellular junction complex, and the functioning of specific epithelial cells, such as enterochromaffin cells and stem cells in pigs. The factors involved include microbial metabolites, especially short-chain fatty acids and host-microbe co-metabolism. Recent studies have revealed the essential role of amino acid metabolism in regulating the gut microbiome and epithelial barrier. This chapter discusses how the pig gut microbiome modulates epithelial structure and function, highlighting findings that reflect the relationship between the gut microbiome, intestinal structure and function.

Newborn Screening in Japan—2021

Japan’s Newborn Mass Screening (NBS) was started in 1977 for amino acid metabolism disorders (phenylketonuria (PKU), homocystinuria, maple syrup urine, histidineemia (discontinued in 1993)) and galactosemia at the national level as a national project [...]

Amino Acid Metabolism in Cancer Drug Resistance

Despite the numerous investigations on resistance mechanisms, drug resistance in cancer therapies still limits favorable outcomes in cancer patients. The complexities of the inherent characteristics of tumors, such as tumor heterogeneity and the complicated interaction within the tumor microenvironment, still hinder efforts to overcome drug resistance in cancer cells, requiring innovative approaches. In this review, we describe recent studies offering evidence for the essential roles of amino acid metabolism in driving drug resistance in cancer cells. Amino acids support cancer cells in counteracting therapies by maintaining redox homeostasis, sustaining biosynthetic processes, regulating epigenetic modification, and providing metabolic intermediates for energy generation. In addition, amino acid metabolism impacts anticancer immune responses, creating an immunosuppressive or immunoeffective microenvironment. A comprehensive understanding of amino acid metabolism as it relates to therapeutic resistance mechanisms will improve anticancer therapeutic strategies.