The Na+/H+ Exchanger Controls Deoxycholic Acid-Induced Apoptosis by a H+-Activated, Na+-Dependent Ionic Shift in Esophageal Cells

Apoptosis resistance is a hallmark of cancer cells. Typically, bile acids induce apoptosis. However during gastrointestinal (GI) tumorigenesis the cancer cells develop resistance to bile acid-induced cell death. To understand how bile acids induce apoptosis resistance we first need to identify the molecular pathways that initiate apoptosis in response to bile acid exposure. In this study we examined the mechanism of deoxycholic acid (DCA)-induced apoptosis, specifically the role of Na+/H+ exchanger (NHE) and Na+ influx in esophageal cells. In vitro studies revealed that the exposure of esophageal cells (JH-EsoAd1, CP-A) to DCA (0.2 mM -0.5 mM) caused lysosomal membrane perturbation and transient cytoplasmic acidification. Fluorescence microscopy in conjunction with atomic absorption spectrophotometry demonstrated that this effect on lysosomes correlated with influx of Na+, subsequent loss of intracellular K+, an increase of Ca2+ and apoptosis. However, ethylisopropyl-amiloride (EIPA), a selective inhibitor of NHE, prevented Na+, K+ and Ca2+ changes and caspase 3/7 activation induced by DCA. Ouabain and amphotericin B, two drugs that increase intracellular Na+ levels, induced similar changes as DCA (ion imbalance, caspase3/7 activation). On the contrary, DCA-induced cell death was inhibited by medium with low a Na+ concentrations. In the same experiments, we exposed rat ileum ex-vivo to DCA with or without EIPA. Severe tissue damage and caspase-3 activation was observed after DCA treatment, but EIPA almost fully prevented this response. In summary, NHE-mediated Na+ influx is a critical step leading to DCA-induced apoptosis. Cells tolerate acidification but evade DCA-induced apoptosis if NHE is inhibited. Our data suggests that suppression of NHE by endogenous or exogenous inhibitors may lead to apoptosis resistance during GI tumorigenesis

The high-resolution imaging science experiment (HiRISE) in the MRO extended science phases (2009–2023)

The Mars Reconnaissance Orbiter has been orbiting Mars since 2006 and has acquired >80,000 HiRISE images with sub-meter resolution, contributing to over 2000 peer-reviewed publications, and has provided the data needed to enable safe surface landings in key locations by several rovers or landers. This paper describes the changes to science planning, data processing, and analysis tools since the initial Primary Science Phase in 2006–2008. These changes affect the data used or requested by the community and how they should interpret the data. There have been a variety of complications to the dataset over the years, such as gaps in monitoring due to spacecraft and instrument issues and special events like the arrival of new landers or rovers on Mars or global dust storms. The HiRISE optics have performed well except for a period when temperature uniformity was perturbed, reducing the resolution of some images. The focal plane system now has 12 rather than 14 operational detectors. The first failure (2011) was a unit at the edge of the swath width, reducing image width by 10% rather than creating a gap. The recent (2023) failure was in the middle of the swath. An unusual problem with the analog-to-digital conversion of the signal (resulting in erroneous data) has worsened over time; mitigation steps so far have preserved full-resolution imaging over all functional detectors. Soon, full-resolution imaging will be narrowed to a subset of the detectors and there will be more 2 × 2 binned data. We describe lessons received for future very high-resolution orbital imaging. We continue to invite all interested people to suggest HiRISE targets on Mars via HiWish, and to explore the easy-to-use publicly available images.</p