Thioredoxin 1 is upregulated in the bone and bone marrow following experimental myocardial infarction: evidence for a remote organ response

José R Godoy,Eva-Maria Hanschmann,Sarah Pittrich,Reinhold G Erben,Christopher Horst Lillig,Svetlana Slavic

doi:10.1007/s00418-020-01939-w

Abstract

Ischemia and reperfusion events, such as myocardial infarction (MI), are reported to induce remote organ damage severely compromising patient outcomes. Tissue survival and functional restoration relies on the activation of endogenous redox regulatory systems such as the oxidoreductases of the thioredoxin (Trx) family. Trxs and peroxiredoxins (Prxs) are essential for the redox regulation of protein thiol groups and for the reduction of hydrogen peroxide, respectively. Here, we determined whether experimental MI induces changes in Trxs and Prxs in the heart as well as in secondary organs. Levels and localization of Trx1, TrxR1, Trx2, Prx1, and Prx2 were analyzed in the femur, vertebrae, and kidneys of rats following MI or sham surgery. Trx1 levels were significantly increased in the heart (P = 0.0017) and femur (P < 0.0001) of MI animals. In the femur and lumbar vertebrae, Trx1 upregulation was detected in bone-lining cells, osteoblasts, megakaryocytes, and other hematopoietic cells. Serum levels of Trx1 increased significantly 2 days after MI compared to sham animals (P = 0.0085). Differential regulation of Trx1 in the bone was also detected by immunohistochemistry 1 month after MI. N-Acetyl-cysteine treatment over a period of 1 month induced a significant reduction of Trx1 levels in the bone of MI rats compared to sham and to MI vehicle. This study provides first evidence that MI induces remote organ upregulation of the redox protein Trx1 in the bone, as a response to ischemia–reperfusion injury in the heart.

Highlights

Remote organ damage secondary to ischemia reperfusion (IR) injury is a common complication that substantially worsens the prognosis of critically ill patients
We proposed that upregulation of redox regulatory systems such as Trxs and Prxs may occur in the bone marrow as a response to IR injury in the heart
The peripheral localization of Trx1 we observed in megakaryocytes of Myocardial infarction (MI) animals together with the significant increase in serum we found 2 days after MI may provide support to this hypothesis

Summary

Introduction

Remote organ damage secondary to ischemia reperfusion (IR) injury is a common complication that substantially worsens the prognosis of critically ill patients. Oxidoreductases of the thioredoxin family of proteins, among others thioredoxins (Trxs) and peroxiredoxins (Prxs), are recognized as key molecules in redox signaling regulating oxidative post-translational modifications of protein thiol groups as well as cellular levels of hydrogen peroxide (Lillig and Holmgren 2007; Hanschmann et al 2013). We proposed that upregulation of redox regulatory systems such as Trxs and Prxs may occur in the bone marrow as a response to IR injury in the heart. We show a detailed analysis of the localization of redox proteins in the bone and bone marrow of rats and provide, for the first time, evidence for an upregulation of Trx in the bone and bone marrow as a response to IR injury in the heart. Heart, kidney, femur and lumbar vertebrae were removed and processed for immunohistochemistry, RTPCR, Western blot or ELISA

Materials and methods

Results

Discussion

Compliance with ethical standards