The lipid biomediator lysophosphatidic acid (LPA) elicits a unique response in hippocampal neurons, LPA induces neuronal apoptosis. This study explores the effects of LPA on cells with neuronal properties, nerve growth factor-differentiated PC6 cells, a clone of PC12 cells. LPA induced apoptosis in these cells as assessed by chromatin condensation, terminal dUTP nick end-labeling of DNA, protection against these nuclear alterations by a general caspase inhibitor and the lack of release of lactic dehydrogenase. LPA caused oxidative stress, namely a decreased reduction of MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. This oxidative stress appears to be of functional significance, since cells were protected by pretreatment with the antioxidant propyl gallate and by stable transfection with cDNA encoding the antioxidant enzyme, manganese superoxide dismutase. Mitochondrial and nitric oxide participation in LPA-induced apoptosis are suggested by the protection afforded by pretreatment with either cyclosporin A, an inhibitor of mitochondrial permeability transition, or nitric oxide synthase inhibitors. The nitric oxide synthase inhibitor findings are novel, since to our knowledge, LPA has not heretofore been associated with an increase in nitric oxide. In addition, as observed for many neurotoxic agents, insulin-like growth factor I protected against LPA-induced apoptosis of PC6 cells.

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We described three uses of energy for which greater efficiency is feasible: transportation, space heating, and air conditioning. Shifts to less energy-intensive transportation modes could substantially reduce energy consumption; the magnitude of such savings would, of course, depend on the extent of such shifts and possible load factor changes. The hypothetical transportation scenario described here results in a 22 percent savings in energy for transportation in 1970, a savings of 2800 trillion Btu. To the homeowner, increasing the amount of building insulation and, in some cases, adding storm windows would reduce energy consumption and provide monetary savings. If all homes in 1970 had the "economic optimum" amount of insulation, energy consumption for residential heating would have been 42 percent less than if the homes were insulated to meet the pre-1971 FHA standards, a savings of 3100 trillion Btu. Increased utilization of energy-efficient air conditioners and of building insulation would provide significant energy savings and help to reduce peak power demands during the summer. A 67 percent increase in energy efficiency for room air conditioners would have saved 15.8 billion kilowatt-hours in 1970. In conclusion, it is possible-from an engineering point of view-to effect considerable energy savings in the United States. Increases in the efficiency of energy use would provide desired end results with smaller energy inputs. Such measures will not reduce the level of energy consumption, but they could slow energy growth rates.

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