Niggi Iberg

Phosphoinositide 3-kinase C2α is activated upon smooth muscle cell migration and regulated by αvβ3 integrin engagement

The involvement of phosphoinositide 3-kinase C2α in vascular smooth muscle cell migration was investigated. Products of phosphoinositide 3-kinase, phosphatidylinositol-3-phosphate, and phosphatidylinositol-3,4-bis-phosphate were increased upon smooth muscle cell migration but their synthesis was affected only partially by phosphoinositide 3-kinase inhibitors, wortmannin and LY-294002. Using specific antibody, we showed that the wortmannin/LY-294002 poorly sensitive phosphoinositide 3-kinase C2α is expressed in smooth muscle cells. Measurement of phosphoinositide 3-kinase C2α activity in vitro, after immunoprecipitation, clearly demonstrated its activation upon smooth muscle cell migration. Moreover, for the first time, phosphoinositide 3-kinase C2α was found to be differentially regulated by α v β 3 and α v β 5 integrin engagement. Finally, we have identified two new potential phosphoinositide 3-kinase C2α-binding proteins, p70 and p110, which both may be tyrosine phosphorylated. Thus, phosphoinositide 3-kinase C2α might represent a new regulatory pathway of cell migration downstream of integrin engagement.

Identification of a sulfated tetrasaccharide with heparin-like antiproliferative activity

Abstract Investigation of the smooth muscle cell antiproliferative activities of Trestatin A sulfate substructures showed that a sulfated pentasaccharide is required to maintain a heparin-like effect. The modification of one glycosidic bond led to a synthetically readily available tetrasaccharide, namely sulfated β-maltosyl trehalose12, with similar antiproliferative but devoid of anticoagulant acitivity.

The heparin-like antiproliferative activity of sulfated tetrasaccharides is sensitive to structural variation

Abstract The sulfated tetrasaccharide β-maltosyl-(1→4)-α,α-trehalose 2 with high antiproliferative activity on smooth muscle cells was modified in the maltosyl moiety by linking eight different disaccharides equatorially to trehalose; the biological activity varied strongly between different structures.

Selectively deoxygenated sulfated tetrasaccharides as probes for the investigation of smooth muscle cell antiproliferative activity

Abstract Selectively deoxygenated analogues of highly (ca. 80 %) sulfated β-maltosyl-(1→4)-α,α-trehalose were investigated to map the importance of the individual sulfates for biological activity. Single deoxygenations led to activity losses up to 30 %; the essential sulfates are located on the outer glucopyranosyl rings of the molecule.

The smooth muscle cell antiproliferative activity of heparan sulfate model oligosaccharides

Abstract Heparan sulfate model oligosaccharides were devised with the simplyfying assumptions that i) carboxyl-reduction and subsequent sulfation of heparan sulfate does not decrease the SMC antiproliferative activity, and ii) N -Sulfates in glucosamines can be replaced by O -sulfates. These heparan sulfate model oligosaccharides are more active than analogous heparin fractions.