RRC ID 44889
著者 Angcajas AB, Hirai N, Kaneshiro K, Karim MR, Horii Y, Kubota M, Fujimura S, Kadowaki M.
タイトル Diversity of amino acid signaling pathways on autophagy regulation: a novel pathway for arginine.
ジャーナル Biochem Biophys Res Commun
Abstract Autophagy is the intracellular bulk degradation process to eliminate damaged cellular machinery and to recycle building blocks, and is crucial for cell survival and cell death. Amino acids modulate autophagy in response to nutrient starvation and oxidative stress. We investigated the relevance of reactive oxygen species (ROS) production on the regulation of autophagy using amino acids, both as a mixture and individually, in rat hepatoma H4-II-E cells. Nutrient starvation elevated ROS production and stimulated autophagy. Treatment with complete (CAA), regulatory (RegAA) and non-regulatory (NonRegAA) amino acid mixtures showed significant suppression of ROS production, whereas only CAA and RegAA exhibited significant suppression of autophagy, suggesting a dissociation of the two responses. The effects of individual amino acids were examined. Leucine from RegAA decreased ROS production and suppressed autophagy. However, methionine and proline from RegAA and arginine, cystine and glutamic acid from NonRegAA suppressed autophagy with an opposite increase in ROS production. Other amino acids from the NonRegAA group showed stimulating effects on ROS production without an autophagic response. Arginine's effect on autophagy suppression was not blocked by rapamycin, indicating an mTOR-independent pathway. Inhibitor studies on arginine-regulated autophagy may indicate the involvement of NO pathway, which is independent from ROS and mTOR pathways.
巻・号 446(1)
ページ 8-14
公開日 2014-3-28
DOI 10.1016/j.bbrc.2014.01.117
PII S0006-291X(14)00152-1
PMID 24486546
MeSH Amino Acids / metabolism* Animals Arginine / metabolism* Autophagy / drug effects Autophagy / physiology* Cell Line Hep G2 Cells Humans Nitric Oxide / metabolism Rats Reactive Oxygen Species / metabolism Signal Transduction Sirolimus / pharmacology TOR Serine-Threonine Kinases / antagonists & inhibitors TOR Serine-Threonine Kinases / metabolism
IF 2.985
引用数 12
WOS 分野 BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 Hep G2