Activation of PKC signaling induces Mg(2+) accumulation in liver cells. To test the hypothesis that PKC induces Mg(2+) accumulation via MAPKs activation, hepatocytes were incubated in the presence of PD98059 and SB202190 as specific inhibitors of ERK1/2 and p38, respectively, and stimulated for Mg(2+) accumulation by addition of PMA or OAG. Accumulation of Mg(2+) within the cells was measured by atomic absorbance spectrophotometry in the acid extract of cell pellet. The presence of either inhibitor completely abolished Mg(2+) accumulation irrespective of the dose of agonist utilized while having no discernible effect on beta -adrenoceptor mediated Mg(2+) extrusion. A partial inhibition on alpha (1)-adrenoceptor mediated Mg(2+) extrusion was observed only in cells treated with PD98059. To confirm the inhibitory effect of PD98509 and SB202190, total and basolateral liver plasma membrane vesicles were purified in the presence of either MAPK inhibitor during the isolation procedure. Consistent with the data obtained in intact cells, liver plasma membrane vesicles purified in the presence of PD98509 or SB202190 lost the ability to accumulate Mg(2+)in exchange for intra-vesicular entrapped Na(+) while retaining the ability to extrude entrapped Mg(2+) in exchange for extra-vesicular Na(+). These data indicate that ERK1/2 and p38 are involved in mediating Mg(2+) accumulation in liver cells following activation of PKC signaling. The absence of a detectable effect of either inhibitor on beta -adrenoceptor induced, Na(+)-dependent Mg(2+) extrusion in intact cells and in purified plasma membrane vesicles further support the hypothesis that Mg(2+) extrusion and accumulation occur through distinct and differently regulated transport mechanisms.
As part of NASA's new deep space exploration system, the Space Launch System (SLS) will provide the United States with guaranteed access to deep space and an unparalleled capability for launching primary and co-manifested payloads beyond Earth's orbit. Planned missions for the new SLS family of vehicles include launching the Orion spacecraft and elements of the new Gateway astronaut-tended outpost to lunar orbit and sending robotic probes deep into the solar system, such as to Jupiter's moon Europa. If mission parameters allow, secondary payloads in 6U, 12U or larger sizes will also have rideshare opportunities, providing CubeSats with access to deep space. The SLS vehicle will evolve into progressively more powerful variants with fairings in several sizes available to meet an array of mission needs. Superior mass, volume and characteristic energy (C3) enable sending larger, heavier payloads to a variety of destinations. Several elements of the Block 1 vehicle for the first mission, Exploration Mission-1 (EM-1) are complete and have been delivered to the Exploration Ground Systems (EGS) Program at Kennedy Space Center (KSC), which has responsibility for integrating and launching the vehicle. Contractors are already at work manufacturing the second Block 1 vehicle and incorporating numerous lessons learned in manufacturing America's first super heavy-lift deep space rocket since the Apollo Program's Saturn V enabled humankind to take a giant leap forward.
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