Justice and Negotiation.

This review article examines the literature regarding the role played by principles of justice in negotiation. Laboratory experiments and high-stakes negotiations reveal that justice is a complex concept, both in relation to attaining just outcomes and to establishing just processes. We focus on how justice preferences guide the process and outcome of negotiated exchanges. Focusing primarily on the two types of principles that have received the most attention, distributive justice (outcomes of negotiation) and procedural justice (process of negotiation), we introduce the topic by reviewing the most relevant experimental and field or archival research on the roles played by these justice principles in negotiation. A discussion of the methods used in these studies precedes a review organized in terms of a framework that highlights the concept of negotiating stages. We also develop hypotheses based on the existing literature to point the way forward for further research on this topic.

Domain V peptides inhibit beta2-glycoprotein I-mediated mesenteric ischemia/reperfusion-induced tissue damage and inflammation.

Reperfusion of ischemic tissue induces significant tissue damage in multiple conditions, including myocardial infarctions, stroke, and transplantation. Although not as common, the mortality rate of mesenteric ischemia/reperfusion (IR) remains >70%. Although complement and naturally occurring Abs are known to mediate significant damage during IR, the target Ags are intracellular molecules. We investigated the role of the serum protein, ß2-glycoprotein I as an initiating Ag for Ab recognition and ß2-glycoprotein I (ß2-GPI) peptides as a therapeutic for mesenteric IR. The time course of ß2-GPI binding to the tissue indicated binding and complement activation within 15 min postreperfusion. Treatment of wild-type mice with peptides corresponding to the lipid binding domain V of ß2-GPI blocked intestinal injury and inflammation, including cellular influx and cytokine and eicosanoid production. The optimal therapeutic peptide (peptide 296) contained the lysine-rich region of domain V. In addition, damage and most inflammation were also blocked by peptide 305, which overlaps with peptide 296 but does not contain the lysine-rich, phospholipid-binding region. Importantly, peptide 296 retained efficacy after replacement of cysteine residues with serine. In addition, infusion of wild-type serum containing reduced levels of anti-ß2-GPI Abs into Rag-1(-/-) mice prevented IR-induced intestinal damage and inflammation. Taken together, these data suggest that the serum protein ß2-GPI initiates the IR-induced intestinal damage and inflammatory response and as such is a critical therapeutic target for IR-induced damage and inflammation.

Normalization of lens protein kinase Cgamma in galactosemic dogs by a novel aldose reductase inhibitor.

The purpose of this study was to determine the effects of a novel aldose reductase inhibitor on lens protein kinase Cgamma (PKCgamma) levels in galactosemic dogs. Six-month old Beagles (12 total; 6 male and 6 female) were made galactosemic by feeding a diet of 40% galactose for 6 weeks. Three dogs per group were fed either control, normal diet, 40% galactose diet, 40% galactose diet with aldose reductase inhibitor at 100 mg/kg body weight per day given orally, or a control diet with aldose reductase inhibitor alone (1-H,7-H-5alpha,6,8,9-tetrahydro-1-oxopyran[4,3-beta](1) benzopyran, referred to herein as HAR-1). Lenses were removed and analyzed for toxicity by pathological examination. Lens polyol concentrations were determined by GC/MS. PKCgamma levels were determined by Western blot and by reverse transcriptase-polymerase chain reaction (RT-PCR). No toxicity was observed from the aldose reductase inhibitor when given at 100 mg/kg body weight per day for 6 weeks. Galactosemic dogs showed deterioration of lens cells. Deterioration included vacuole formation in the lens, cell lysis, and loss of cell nuclei. Galactosemic dogs given the HAR-1 appeared identical to control dogs. Polyol concentrations in the lenses were reduced by 50% in dogs fed the 40% galactose diet with the aldose reductase inhibitor, HAR-1. PKCgamma protein levels were reduced in the galactosemic dog lenses, but synthesis of PKCgamma was not affected, as measured by RT-PCR. The PKCgamma protein levels were similar to controls in dogs given the aldose reductase inhibitor, HAR-1, even when polyol concentrations remained 50% elevated above control levels. HAR-1, when given to control dogs, caused a reduction in the synthesis of PKCgamma mRNA but not in total PKCgamma protein levels. This study demonstrates the use of a novel aldose reductase inhibitor to control changes in PKCgamma in dog lens, a PKC that is known to control gap junction activity.

LEDGF activation of PKC gamma and gap junction disassembly in lens epithelial cells.

Lens epithelium-derived growth factor (LEDGF) has been shown to enhance survival of lens epithelial cells (LECs) against stress. The objectives of these studies are to determine how LEDGF controls PKC gamma activity in normal LECs: how this control of PKC gamma regulates the phosphorylation of Connexin 43, the inhibition of gap junction activity, and the prevention of assembly of gap junctions in LECs. A rabbit LEC line, N/N1003A, was grown in the absence or presence of LEDGF. PKC gamma protein was translocated from the cytosolic fractions to the membrane fractions upon addition of LEDGF at 10 ng ml(-1). In whole cell extracts of N/N1003A cells, co-immunoprecipitation assays showed a protein-protein interaction between PKC gamma and Connexin 43. In the presence of LEDGF the activation of PKC gamma enhanced the phosphorylation of Connexin 43 by four-fold compared to the absence of LEDGF. The addition of LEDGF for 30 min resulted in a 65% decrease in gap junction Connexin 43 at the cell surface and a 70% decrease in gap junction activity. These results suggest that the activation of PKC gamma by LEDGF plays a major role in gap junction assembly/disassembly, which may enhance survival of LECs against osmolarity-stress induced by high sugar concentration.

The interaction and phosphorylation of tropomodulin by protein kinase Calpha in N/N 1003A lens epithelial cells.

PURPOSE: Tropomodulin, a tropomyosin and actin-binding protein stabilizes tropomyosin-actin filaments and is important in maintaining the elongated shape of lens fiber cells. In this study the role of PKCalpha-catalyzed phosphorylation of tropomodulin is determined. METHODS: The interaction of PKCalpha and tropomodulin was measured by immunoprecipitation after activation with either phorbol ester at 200 nM for 60 min or 10 ng/ml EGF for 15 min. Tropomodulin phosphorylation was determined after co-immunoprecipitation using an in vitro [gamma-32P] PKC activity assay and by specific reaction with antiphosphothreonine antisera. Changes in tropomodulin interaction with tropomyosin or with the cytoskeleton were measured in a gel overlay assay and by association with a "Triton-insoluble" fraction. RESULTS: Both phorbol ester and EGF caused an increased interaction of PKCalpha with tropomodulin. Following activation of PKCalpha by phorbol ester or by EGF there was an increased phosphorylation of tropomodulin on threonine residues. The phosphorylation of tropomodulin did not affect interaction with tropomyosin as measured by a gel overlay assay. However, there was an increased association of tropomodulin with the "Triton-insoluble" cytoskeletal fraction. CONCLUSIONS: Activation of PKCalpha by EGF causes an increased phosphorylation of tropomodulin which results in an increase in tropomodulin association with cytoskeletal components. This establishes a signal pathway by which EGF induced activation of PKCalpha alters the interaction of lens cytoskeletal proteins.

Effect of protein kinase Cgamma on gap junction disassembly in lens epithelial cells and retinal cells in culture.

PURPOSE: To determine the effects of protein kinase Cgamma (PKCgamma) on phosphorylation of Cx43, the gap junction protein of lens epithelial cells, and on cell surface assembly/disassembly of Cx43-gap junction complexes. METHODS: Association and phosphorylation of Cx43 by PKCgamma was determined using co-immunoprecipitation and reaction with phosphoserine antisera. Activation of PKCgamma was with 200 nM phorbol ester for 30 to 60 min. Effects of specific PKC isoforms was determined after overexpression of either PKCalpha or PKCgamma for 24 h in N/N 1003A rabbit lens epithelial cells or in two retinal cell lines, WERI and Y79. Gap junction plaques were counted on the cell surface by immunolabeling of Cx43 using confocal microscopy. RESULTS: Co-immunoprecipitation of Cx43 with PKCgamma was observed only in cells over expressing PKCgamma and in cells activated with phorbol ester. Both overexpression and phorbol ester produced a rapid phosphorylation of Cx43 on serine. Cx43 cell surface gap junction plaques decreased in cells over expressing PKCgamma and in cells treated with phorbol ester. Similar results were observed using the retinal cell lines, WERI and Y79. The effect of PKCgamma overexpression was persistent for 7 days but total cell Cx43 was not decreased. Overexpression of PKCa resulted in an increase in cell surface gap junction plaques. CONCLUSIONS: PKCgamma can be co-immunoprecipitated with Cx43 from lens epithelial cells using phorbol ester activation. PKCgamma phosphorylates Cx43 on serine and this causes disassembly and loss of gap junction Cx43 from the cell surface. Overexpression of PKCgamma confirmed that only this PKC isoform caused the loss of cell surface Cx43. Overexpression of PKCalpha, the other major lens PKC isoform, caused an increase in cell surface Cx43. The presence of PKCgamma and loss of surface Cx43 from two retinal cell lines, WERI and Y79, upon phorbol ester activation further suggests that activation of PKCgamma may be a common mechanism for control of cell surface Cx43.