Phenylac-Gly-OH is a glycine conjugate of phenylacetate. The intestinal microbiota converts phenylpyruvate into phenylacetic acid, and under the catalysis of liver and kidney enzymes, phenylacetic acid combines with glycine to form Phenylac-Gly-OH[1].
Phenylac-Gly-OH induced the expression of natriuretic peptide precursor B gene (Nppb) in immortalized rat adult myocardial H9c2 cells, and the expression level of Nppb in the Phenylac-Gly-OH group was 3.66-fold higher than that in the vector group[2]. Phenylac-Gly-OH (100 μM) reduces hypoxia-induced apoptosis of neonatal mouse cardiomyocytes and activates the anti-apoptotic Gαi/PI3K/AKT signaling cascade in NMCMs cells by stimulating β2 adrenergic receptor (β2AR) signaling[3].
After intraperitoneal injection of Phenylac-Gly-OH (50 mg/kg) for 15min in male C57BL6/J mice, the expression of Nppb in left atrium of mice in Phenylac-Gly-OH group was significantly increased (1.46 times) compared with mice treated with carriers[2]. In mice with FeCl3-induced carotid artery injury, Phenylac-Gly-OH (50 mg/kg) induced an increase in platelet thrombosis in the injured carotid artery compared with mice treated with the nutritional precursor phenylalanine (Phe) or normal saline (carrier). And correspondingly reduce the blood flow stopping time (i.e. occlusion time) after injury[4].
References:
[1] Zhu Y, Dwidar M, Nemet I, et al. Two distinct gut microbial pathways contribute to meta-organismal production of phenylacetylglutamine with links to cardiovascular disease[J]. Cell host & microbe, 2023, 31(1): 18-32. e9.
[2] Romano K A, Nemet I, Prasad Saha P, et al. Gut microbiota-generated phenylacetylglutamine and heart failure[J]. Circulation: Heart Failure, 2023, 16(1): e009972.
[3] Xu X, Lu W, Shi J, et al. The gut microbial metabolite phenylacetylglycine protects against cardiac injury caused by ischemia/reperfusion through activating β2AR[J]. Archives of Biochemistry and Biophysics, 2021, 697: 108720.
[4] Nemet I, Saha P P, Gupta N, et al. A cardiovascular disease-linked gut microbial metabolite acts via adrenergic receptors[J]. Cell, 2020, 180(5): 862-877. e22.
Phenylac-Gly-OH是苯乙酸酯的甘氨酸偶联物。肠道微生物群将苯丙酮酸转化为苯乙酸，在肝酶和肾酶的催化作用下，苯乙酸与甘氨酸结合形成Phenylac-Gly-OH[1]。
Phenylac-Gly-OH可诱导永生化大鼠成心肌H9c2细胞中利钠肽前体B基因（Nppb）的表达，Phenylac-Gly-OH组Nppb的表达水平是载体组的3.66倍[2]。Phenylac-Gly-OH（100 μM）降低缺氧诱导的新生小鼠心肌细胞凋亡，并通过刺激β2 肾上腺素能受体（β2AR）信号传导激活NMCMs细胞中的抗凋亡Gαi/PI3K/AKT信号级联反应[3]。
C57BL6/J雄性小鼠腹腔注射Phenylac-Gly-OH（50 mg/kg）15min后，与载体处理的小鼠相比，Phenylac-Gly-OH组小鼠左心房中的Nppb表达显著增加（1.46倍）[2]。在FeCl3 诱导的颈动脉损伤的小鼠中，与用营养前体苯丙氨酸（Phe）或生理盐水（载体）处理的小鼠相比，Phenylac-Gly-OH（50 mg/kg）诱导了受伤颈动脉内血小板血栓形成的增加，并相应地减少受伤后血流停止时间（即闭塞时间）[4]。