However, we did not observe a change in phosphorylation of ACC, an indicator of AMPK activity and an important pathway by which AMPK increases fatty acid oxidation. This may not actually be that surprising, since AMPK activation can decrease proliferation but as we show here oleate protects against the drop in proliferation induced by palmitate. It is still a possibility, however, that a reduction in glycolysis may be involved in palmitate-induced BMMSC death, but changes in glycolysis that occur in response to 24 hr treatment with palmitate and/or oleate were masked by switching all groups to the same buffer during the measurement of glycolysis rates. Oleate had a dramatic effect of preventing palmitate-induced BMMSC death. This may have occurred secondary to inhibiting palmitate uptake. Acutely, oleate and palmitate reduced each other��s uptake. However, after 24 hr of exposure to palmitate and/or oleate, palmitate uptake was not different DLPC between groups. It is still possible, however, that oleate did in fact reduce palmitate uptake at 24 hr but it was an acute effect and therefore was not measured. Therefore, oleate may be at least partially protecting against palmitate-induced cell death by reducing intracellular palmitate BMS 195614 levels by decreasing palmitate uptake. Another potential mechanism for palmitate-induced cell death in the BMMSCs is the potential involvement of ceramides. Elevated levels of ceramides are able to induce death in a number of different cell types. The fact that saturated fatty acids, which are ceramide substrates, induced BMMSC death while oleate, an unsaturated fatty acid which is not a ceramide substrate, does not induce BMMSC death suggests that ceramides could be involved in saturated fatty acid-induced BMMSC death. In addition, chronic exposure to palmitate reduces fatty acid oxidation, which could result in a redirection of palmitate into ceramides. Further, oleate prevented this drop in fatty acid oxidation and decreased palmitate uptake, which could decrease ceramide production by reducing the amount of palmitate present to be used in ceramide production. In fact, elevated ceramide levels accompany the palmitate- induced reduction in fatty acid oxidation in neonatal cardiac myocytes. Unfortunately, experimental conditions precluded us from measuring ceramide levels in these cells. However, there is evidence that palmitate at least does not always work through ceramides to induce cell death. During the last several decades, the incidence of esophageal squamous cell carcinoma has been declining. However, ESCC remains the predominant carcinoma in many countries of east and central Asia. Esophageal cancer, which accounted for 482,300 new cases of cancer in 2008, is the eighth most common cancer worldwide, and has the sixth highest incidence of cancer mortality, with 406,800 deaths registered.