Response to chronic sustained hypoxia: increased cytosolic gelsolin and decreased plasma gelsolin levels

Abstract

An actin binding protein, gelsolin (GSN) has two isoforms, plasma (pGSN) and cytosolic (cGSN). Changes in pGSN and/or cGSN levels have been shown to be associated with the pathogenesis of several diseases. The aim of this study was to evaluate changes in intracellular and extracellular GSNlevels with HIF-1 in animals exposed to chronic sustained hypoxia (CSH), in addition to apoptosis and the cellular redox status. The rats in the Sham group were exposed to 21% O₂, and the rats in the hypoxia groups were exposed to 13 and 10% O₂, respectively. Plasma pGSN, HIF-1α, Total Antioxidant Status (TAS) and Total Oxidant Status (TOS), and lung tissue pGSN, HIF-1α, TAS, TOS, GSN levels, and apoptotic cell numbers were measured. HIF-1α levels were found to increase significantly in the tissue, especially in the group with severe hypoxia, both in biochemical and histological examinations. pGSN levels were also significantly decreased in both plasma and tissue. Significant increases in tissue were observed in cGSN. It was observed that while the antioxidant activity was dominant in the tissue, the oxidant activity was dominant in the plasma. In particular, the response to hypoxia regulated by HIF-1 is very important for cellular survival. The results of this study showed that the increase in cGSN and TAS levels in the lung tissue together with HIF-1α can be considered as the activation of mechanisms for cellular protection.

Keywords: Apoptosis; Chronic sustained hypoxia; Cytosolic gelsolin; HIF-1; Oxidative stress; Plasma gelsolin.