27 research outputs found

    Phospholipase D signaling: orchestration by PIP2 and small GTPases

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    Hydrolysis of phosphatidylcholine by phospholipase D (PLD) leads to the generation of the versatile lipid second messenger, phosphatidic acid (PA), which is involved in fundamental cellular processes, including membrane trafficking, actin cytoskeleton remodeling, cell proliferation and cell survival. PLD activity can be dramatically stimulated by a large number of cell surface receptors and is elaborately regulated by intracellular factors, including protein kinase C isoforms, small GTPases of the ARF, Rho and Ras families and, particularly, by the phosphoinositide, phosphatidylinositol 4,5-bisphosphate (PIP2). PIP2 is well known as substrate for the generation of second messengers by phospholipase C, but is now also understood to recruit and/or activate a variety of actin regulatory proteins, ion channels and other signaling proteins, including PLD, by direct interaction. The synthesis of PIP2 by phosphoinositide 5-kinase (PIP5K) isoforms is tightly regulated by small GTPases and, interestingly, by PA as well, and the concerted formation of PIP2 and PA has been shown to mediate receptor-regulated cellular events. This review highlights the regulation of PLD by membrane receptors, and describes how the close encounter of PLD and PIP5K isoforms with small GTPases permits the execution of specific cellular functions

    Influencing factors on the suitability of organ-cultured corneas.

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    International audiencePURPOSE: To determine the factors related to donor and tissue retrieval, which influence the suitability of organ-cultured corneas for transplantation. PATIENTS AND METHODS: We retrospectively analysed 2596 donor corneas. Polytomic logistic regression analysis was used to assess the influence of various factors (that is, donor age, cause of death, death-to-tissue retrieval time, tissue retrieval-to-reception time, and tissue retrieval method) on the suitability of grafts for transplantation. Positive predictive values (PPVs) were computed. RESULTS: Forty-three percent (1118/2596) of corneas were discarded. The leading cause for discarding corneas was poor endothelial quality (21.5%). Corneas from donors older than 80 years were more likely to be discarded because of endothelial insufficiency (OR=2.37, P=0.001). Longer time between death and tissue retrieval was associated with increased risk of positive serology (OR=1.43, P=0.02). Increased time between tissue retrieval and reception was associated with increased risk of contamination (OR=1.57, P=0.03). PPV increased from 38.5% for corneas retrieved from donors older than 80 years featuring a death-to-tissue retrieval time of more than 6 h and a tissue retrieval-to-reception time of more than 24 h to 64.7% for corneas retrieved from donors younger than 80 years featuring a death-to tissue retrieval time shorter than 6 h and a tissue retrieval-to-reception time shorter than 24 h. CONCLUSION: The percentage of discarded corneas can be reduced by including donors aged 80 years or less, using a time from donor's death to tissue retrieval shorter than 6 h, and a tissue retrieval-to-reception time shorter than 24 h
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