Serum Glucocorticoid-Regulated Kinase-1 in Ischemia-Reperfusion Injury: Blessing or Curse

The family of serum-glucocorticoid-regulated kinase (SGK) consists of three paralogs, SGK-1, SGK-2, and SGK-3, with SGK-1 being the better studied. Indeed, recognition of the role of SGK-1 in regulation of cell survival and proliferation has led to introduction of a number of small-molecule inhibitors for some types of cancer. In addition, SGK-1 regulates major physiologic effects, such as renal solute transport, and contributes to the pathogenesis of non-neoplastic conditions involving major organs including the heart and the kidney. These observations raise the prospect for therapeutic modulation of SGK-1 to reduce the burden of such diseases as myocardial infarction and acute kidney injury. Following a brief description of the structure and function of SGK family of proteins, the present review is primarily focused on our current understanding of the role of SGK-1 in pathologies related to ischemia-reperfusion injury involving several organs (e.g., heart, kidney). The essential role of the mitochondrial permeability transition pore in cell death coupled with the pro-survival function of SGK-1 raise the prospect that its therapeutic modulation could beneficially impact conditions associated with ischemia-reperfusion injury.