title: Nur77 is involved in graft infiltrating T lymphocyte apoptosis in rat cardiac transplantation model.
abstract: Acute allograft rejection is initiated by a large number of recipient T cells that recognize donor alloantigens. Apoptotic signals trigger Nur77 production. Nur77 translocates from the nucleus to the mitochondria to induce a loss of mitochondrial membrane potential and the release of mitochondrial cell-death mediators, including HtrA2/Omi. In this study, we investigated the relationship between Nur77, HtrA2/Omi, and T lymphocyte apoptosis during acute allograft rejection in a rat cardiac transplantation model. The median survival time of the isograft group was longer than that of the allograft group. The cardiac grafts in isogenic (Lewis to Lewis) and allogenic (Wistar to Lewis) models were subjected to HE stain, showing that no rejection occurred in the isografts and that the rejection level was increased in allografts. Compared with the rare expression in syngeneic Lewis rat hearts by western blot analysis, Nur77 protein level in allograft increased from day 1, peaked at day 5 after transplantation, and maintained the highest level until day 7. Double immunofluorescence staining on allograft tissues at day 5 showed Nur77 immunocompetence in most CD3(+) cells, and Nur77 positive T cells also showed HtrA2/Omi-positive signal. Meanwhile, active caspase-3 was apparent in these HtrA2/Omi-positive T cells. Immunohistochemical results suggested that both Nur77 and active caspase-3 were expressed in increasing infiltrating lymphocytes. Our results demonstrated that upregulated Nur77 may promote graft-infiltrating T lymphocyte apoptosis by translocating and inducing HtrA2/Omi release from mitochondria in acute rejection after cardiac transplantation.
authors.affiliation: Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, PR China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu 226001, PR China.
authors.forename: Jiahai
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, PR China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu 226001, PR China.
authors.forename: Kunpeng
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, PR China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu 226001, PR China.
authors.forename: Xuechao
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, PR China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu 226001, PR China.
authors.forename: Daliang
authors.initials: D
authors.lastname: Yan
authors.affiliation: Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, PR China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu 226001, PR China.
authors.forename: Long
authors.initials: L
authors.lastname: Qian
authors.affiliation: Department of Vasculocardiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, PR China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu 226001, PR China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, PR China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu 226001, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Vasculocardiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, PR China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu 226001, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Vasculocardiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, PR China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu 226001, PR China. Electronic address: ntwx0513@163.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Pathogen Biology, Medical College, Nantong University, Nantong, Jiangsu 226001, PR China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College, Nantong University, Nantong, Jiangsu 226001, PR China. Electronic address: ntlxj0305@163.com.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Liu
mesh_terms: D000208:Acute Disease; D064591:Allografts; D000818:Animals; D017209:Apoptosis; D017252:CD3 Complex / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016027:Heart Transplantation; D064596:Isografts; D008297:Male; D008929:Mitochondria, Heart / Q000276:immunology / Q000378:metabolism; D009206:Myocardium / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D000068103:Serine-Arginine Splicing Factors; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D017252:CD3 Complex; D009419:Nerve Tissue Proteins; C539820:Nr4a1 protein, rat; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D016601:RNA-Binding Proteins; C490770:Tra2b protein, rat; D000068103:Serine-Arginine Splicing Factors; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: Acute rejection; Cardiac transplantation; HtrA2/Omi; Nur77; T lymphocyte apoptosis