Stress-Induced Proteasome Sub-Cellular Translocation in Cardiomyocytes Causes Altered Intracellular Calcium Handling and Arrhythmias.

The ubiquitin-proteasome system (UPS) is an essential mechanism responsible for the selective degradation of substrate proteins via their conjugation with ubiquitin. Since cardiomyocytes have very limited self-renewal capacity, as they are prone to protein damage due to constant mechanical and metabolic stress, the UPS has a key role in cardiac physiology and pathophysiology. While altered proteasomal activity contributes to a variety of cardiac pathologies, such as heart failure and ischemia/reperfusion injury (IRI), the environmental cues affecting its activity are still unknown, and they are the focus of this work.

Methods for Isolation and Reprogramming of Various Somatic Cell Sources into iPSCs.

Induced pluripotent stem cells (iPSCs) were originally derived from adult somatic cells by ectopic expression of the stem cell transcription factors OCT3/4, SOX2, c-Myc, and KLF4. The characteristic features of iPSCs are similar to those of embryonic stem cells; they can be expanded indefinitely in vitro and differentiated into the three germ layers: endoderm, mesoderm, and ectoderm. The breakthrough discovery by Takahashi and Yamanaka that somatic cells can be "reprogrammed" to generate iPSCs has led to extensive use of iPSCs and their differentiated cells thereof, in diverse research areas, such as regenerative medicine, development, as well as establishment of disease-specific models, thus providing the platform for personalized patient-specific medicine.