title: The novel peptide PACAP-TAT with enhanced traversing ability attenuates the severe lung injury induced by repeated smoke inhalation.
abstract: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a potential therapeutic peptide with anti-inflammatory and anti-oxidative effects. In order to increase the efficiency of traversing biological barriers, a novel fusion peptide PACAP-TAT was produced by tagging PACAP at its C-terminus with 11-amino acid TAT protein transduction domain. The results of characteristic assays showed that PACAP-TAT activated PACAP specific receptor PAC1 with the same potency as PACAP and PACAP-TAT crossed blood-brain barrier (BBB), blood-air barrier (BAB) and blood-testis barrier (BTB) with the efficiency about 2.5-fold higher than that of PACAP. Both PACAP-TAT and PACAP were used treat the mice with lung injury induced by repeated smoke inhalation. It was shown that both PACAP-TAT and PACAP decreased the mortality, increased the body weight and inhibited the edema and vascular permeability in the lungs of the mice received repeated smoke inhalation, while PACAP-TAT displayed more marked effects than PACAP. PACAP-TAT decreased myeloperoxidase (MPO) activity, increased catalase (CAT) activity and down-regulated interleukin 6 (IL-6) and malondialdehyde (MDA) levels in the lungs with a significantly higher efficiency than PACAP. The histopathological analysis also showed that PACAP-TAT attenuated the cell filtration and bronchi epithelial hyperplasia more significantly than PACAP. Moreover the leukocyte count in blood and the serum superoxide dismutase (SOD) activity in the mice treated with PACAP-TAT were significantly different from that in mice treated with PACAP (p<0.05). All these data indicated that PACAP-TAT with increased traversing ability was more effective than PACAP in protecting the mice from the lung injury induced by repeated smoke inhalation.
authors.affiliation: Biomedical Institute of Jinan University, Jinan University, Guangzhou, Guangdong, PR China. rongjie_yu1123@163.com
authors.forename: Rongjie
authors.initials: R
authors.lastname: Yu
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Guo
authors.forename: Lin
authors.initials: L
authors.lastname: Huang
authors.forename: Zhixing
authors.initials: Z
authors.lastname: Zeng
authors.forename: Huahua
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015824:Blood-Air Barrier / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D001814:Blood-Testis Barrier / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D016466:CHO Cells; D002374:Catalase / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D015696:Gene Products, tat / Q000737:chemistry; D055370:Lung Injury / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000737:chemistry / Q000494:pharmacology*; D011654:Pulmonary Edema / Q000188:drug therapy; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000494:pharmacology*; D015208:Smoke Inhalation Injury / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology
chemical_list: C495504:Adcyap1r1 protein, mouse; D015696:Gene Products, tat; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011993:Recombinant Fusion Proteins; D002374:Catalase; D009195:Peroxidase