Inhibition of pulmonary surfactants synthesis during N-methyl-D-aspartate-induced lung injury.
N-methyl-D-aspartate (NMDA) receptors are ionotropic glutamate receptors widely distributed in the central nervous system, and have been extensively investigated for their roles in embryonic development, synaptic plasticity and neuroexcitoxicity. Their functions in the peripheral nervous system and non-neural tissues have caught much attention recently. Over-activation of NMDA receptors induces excitotoxic lung injury. But the endogenous cell types in the lungs that express NMDA receptors remains elusive and the molecular mechanism underlies NMDA-induced lung injury has not been fully characterized. In this work, we reported that functional NMDA receptors were expressed in alveolar type II cells in the lungs. Over-activation of these receptors led to down-regulation of pulmonary surfactants synthesis. We further demonstrated that decreased cellular choline-phosphate cytidylyltransferase alpha expression induced by NMDA treatment accounted for the decreased pulmonary surfactants synthesis. Our results provided important clues for treatment of glutamate lung injury by modulating pulmonary surfactants system.
Shen
Li
L
Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, China.
Li
Lian
L
She
Hua
H
Yue
Shaojie
S
Li
Chen
C
Luo
Ziqiang
Z
D000818:Animals; D045744:Cell Line, Tumor; D018833:Chaperonins / Q000096:biosynthesis; D004794:Enzyme Repression; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D006801:Humans; D055370:Lung Injury / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D016202:N-Methylaspartate / Q000633:toxicity*; D009195:Peroxidase / Q000096:biosynthesis; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism
D018690:Excitatory Amino Acid Agonists; D011663:Pulmonary Surfactants; D016202:N-Methylaspartate; D009195:Peroxidase; D018833:Chaperonins