title: Activation of PRMT1 and PRMT5 mediates hypoxia- and ischemia-induced apoptosis in human lung epithelial cells and the lung of miniature pigs: the role of p38 and JNK mitogen-activated protein kinases.
abstract: Severe hypoxic and ischemic injury leads to primary graft dysfunction after lung transplantation. Arginine methylation, which is responsible for the regulation of a variety of biological functions, is mediated by protein arginine methylation transferases (PRMTs). This study examined the role of hypoxia in PRMT activation in A549 human lung epithelial cells, as well as the role of ischemia in PRMT activation in the lung of miniature pigs. In A459 cells, hypoxia increased the expression of PRMT1 and PRMT5, and overexpression of PRMT1 and PRMT5 induced apoptosis. The transfection of PRMT1 and PRMT5 small interfering RNA (siRNA) prevented hypoxia-inducible factor (HIF)-1α expression and apoptosis in A549 cells. Hypoxia-induced expression of PRMT1 and PRMT5 was blocked by p38 and JNK mitogen-activated protein kinase (MAPK) inhibitors, but not by an inhibitor of extracellular signal-regulated kinases (ERK) 1/2. In the lungs of miniature pigs, ischemia stimulated PRMT1 and PRMT5 expression and induced phosphorylation of p38 MAPK (p-p38), phosphorylation of JNK (p-JNK), and apoptotic molecules. These results demonstrate that PRMT1 and PRMT5 are involved in hypoxia and ischemia-induced apoptosis via p-p38 MAPK and p-JNK in in vitro and in vivo models.
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, South Korea.
authors.forename: Seul Ki
authors.initials: SK
authors.lastname: Lim
authors.forename: Yong Wun
authors.initials: YW
authors.lastname: Jeong
authors.forename: Dong Il
authors.initials: DI
authors.lastname: Kim
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Park
authors.forename: Joo Hee
authors.initials: JH
authors.lastname: Choi
authors.forename: Se Un
authors.initials: SU
authors.lastname: Kim
authors.forename: Seong Soo
authors.initials: SS
authors.lastname: Kang
authors.forename: Ho Jae
authors.initials: HJ
authors.lastname: Han
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis; D004847:Epithelial Cells / Q000201:enzymology / Q000473:pathology; D006801:Humans; D000860:Hypoxia / Q000201:enzymology* / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D007511:Ischemia / Q000201:enzymology* / Q000473:pathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D008168:Lung / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology*; D016040:Lung Transplantation; D011484:Protein-Arginine N-Methyltransferases / Q000096:biosynthesis* / Q000235:genetics; D034622:RNA Interference; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D020545:Respiratory Mucosa / Q000201:enzymology / Q000473:pathology*; D013552:Swine; D013556:Swine, Miniature; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012097:Repressor Proteins; C099988:PRMT1 protein, human; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Apoptosis; Hypoxia; Lung epithelial cells; Mitogen activated protein kinase; PRMT1, 5