Moderate hypothermia induces protein SUMOylation in bone marrow stromal cells and enhances their tolerance to hypoxia

Abstract

Acute cerebral infarction can progress rapidly, and there are limited specific and effective treatments. Small ubiquitin-like modifiers (SUMOs) provide an important post-translational modification of proteins. Following cerebral infarction, multiple proteins can combine with SUMOs to protect nerve cells. Furthermore, moderate hypothermia (core body temperature, 33-34°C) can increase the level of SUMOylation on multiple proteins. In the present study, it was examined whether moderate hypothermia increases the survival rate of bone marrow stromal stem cells (BMSCs) implanted in the cerebral ischemic penumbra via SUMOylation of multiple proteins. Firstly, BMSCs were exposed to oxygen-glucose deprivation (OGD) under moderate hypothermic (33°C) conditions. Subsequently, adult rats with middle cerebral artery occlusion were treated with a combination of BMSCs and moderate hypothermia (32-34°C). The results demonstrated that hypothermia promoted the combination of multiple proteins with SUMOs in BMSCs, and induced transport of SUMOs from the cytoplasm to the nucleus. Moderate hypothermia additionally reduced damage to BMSCs following OGD and improved BMSC survival following transplantation into the penumbra. These data suggest that moderate hypothermia may protect against BMSC injury via rapid SUMOylation of intracellular proteins. Thus, BMSC transplantation combined with moderate hypothermia may be a potential therapeutic strategy to treat cerebral infarction.