Activation of mitogen-activated protein kinases, activator protein-1, and nuclear factor-kappaB during acute rejection after heterotopic heart transplantation in rats.
BACKGROUND
Activation of mitogen-activated protein kinases (MAPKs), including c-Jun NH2-terminal kinases (JNKs), extracellular signal-regulated kinases (ERKs), and p38MAPK during acute cardiac rejection is not clear. This study aimed to determine whether MAPKs and transcriptional factors such as activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB) were involved in acute rejection after cardiac transplantation.


METHODS
Hearts from Lewis (LEW) rats (group C) or DA rats (group R) were transplanted into the abdomen of recipients (LEW). Grafts were collected at the 1st, 3rd, or 5th postoperative day (POD). ERKs were measured by Western blot analysis, and JNKs were measured by in-gel kinase assay. AP-1 and NF-kappaB DNA binding activities were determined using an electrophoretic mobility shift assay. We assessed functions of donor hearts using echocardiography.


RESULTS
Heart rates and myocardial contraction significantly decreased at POD 5 in group R. Phosphorylated p42ERK and p44ERK in the left ventricular free wall (FW) and septal wall (SW) of group R significantly increased at POD 5 compared to those of group C at POD 1. Activities of p46JNK and p55JNK in the FW and SW of group R also significantly increased at POD 5. AP-1 DNA binding activities in the FW and SW of group R significantly increased at POD 5, and NF-kappaB DNA binding activities of group R significantly increased at PODs 3 and 5.


CONCLUSIONS
We conclude that ERK, JNK, AP-1, and NF-kappaB are activated during acute rejection. The MAPK pathways may play an important role in acute cardiac rejection.
Hirai
Hidekazu
H
Department of Cardiovascular Surgery, Osaka City University, Graduate School of Medicine, Japan. hide-hirai@msic.med.osaka-cu.ac.jp
Shibata
Toshihiko
T
Aoyama
Takanobu
T
Yoshiyama
Minoru
M
Omura
Takashi
T
Suehiro
Shigefumi
S
D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D006084:Graft Rejection / Q000209:etiology* / Q000503:physiopathology; D006339:Heart Rate / Q000502:physiology; D016027:Heart Transplantation / Q000009:adverse effects* / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D016328:NF-kappa B / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D018808:Transcription Factor AP-1 / Q000502:physiology*; D016042:Transplantation, Heterotopic
D016328:NF-kappa B; D018808:Transcription Factor AP-1; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases