Showing papers by "Betty Soliven published in 1997"

Characterization of delayed rectifier Kv channels in oligodendrocytes and progenitor cells.

Abstract: We examined the molecular identity of K+ channel genes underlying the delayed rectifier (IK) in differentiated cultured oligodendrocytes (OLGs) and oligodendrocyte progenitor (OP) cells. Using reverse transcription-PCR cloning, we found that OP cells and OLGs expressed multiple Kv transcripts, namely Kv1.2, Kv1.4, Kv.1.5, and Kv1.6. Immunocytochemical and Western blot analyses revealed that Kv1.5 and Kv1.6 as well as Kv1.2 and Kv1.4 channel proteins could be detected in these cells, but definitive evidence for functional K+ channel expression was obtained only for the Kv1.5 channel. In addition, mRNA and immunoreactive protein levels of both Kv1.5 and Kv1.6 channels were significantly lower in differentiated OLGs when compared with levels in OP cells. Proliferation of OP cells was inhibited by K+ channel blockers, but not by incubation with either Kv1.5 or Kv1.6 antisense oligonucleotides. We conclude that (1) IK in OP cells and OLGs is encoded partly by Kv1.5 subunits, possibly forming heteromultimeric channels with Kv1.6 or other Kv subunits; and (2) inhibition of Kv1.5 or Kv1.6 channel expression alone does not prevent mitogenesis. Concomitant inhibition of other Kv channels underlying IK may be necessary for OP cells to exit from cell cycle.

Evaluation of neuropathy in patients on suramin treatment

Abstract: Suramin, a promising chemotherapeutic agent, causes a dose-limiting sensorimotor polyneuropathy. We undertook a phase 1 study of suramin that included serial neurologic and electrophysiologic examinations as part of the safety evaluation. We found that 6 of 41 (15%) patients developed suramin-induced demyelinating neuropathy which resembled Guillain-Barre syndrome clinically. There was 1 asymptomatic patient with electrophysiologic abnormalities suggestive of a demyelinating neuropathy. In addition, 1 patient with mild axonal neuropathy at baseline had deterioration of his symptoms during suramin treatment. Four asymptomatic patients developed electrophysiologic findings suggestive of a mild axonal neuropathy. We conclude that: (1) serial electrophysiologic monitoring is helpful for early detection of suramin-induced neuropathy; and (2) fixed dosing schedule of suramin without adaptive control does not lead to an increased incidence of demyelinating neuropathy when compared to adaptively controlled dosing schedules.

Arachidonic acid inhibits myelin basic protein phosphorylation in cultured oligodendrocytes

Abstract: Protein phosphorylation is a well-known mechanism by which extracellular molecules or factors transduce their signals into intracellular effects. In the context of myelin assembly, phosphorylation of major myelin proteins affects the electrostatic repulsion between adjacent proteins within myelin structure and therefore constitutes one of the mechanisms by which myelin stability is regulated. We report here that arachidonic acid (AA) decreases the phosphorylation of myelin basic protein (MBP) both in the absence and in the presence of phorbol esters in cultured rat oligodendrocytes (OLGs). The effect of AA on MBP phosphorylation is not mediated by cyclooxygenase products, though the possibility that leukotrienes or other epoxides may have a role cannot be excluded. AA did not act by inactivation of protein kinase C. Based on our findings from gadolinium and low K+ experiments, we conclude that inhibition of MBP phosphorylation is not dependent on AA-induced increases in OLG Ca(i), but rather on its depolarizing action. We have thus demonstrated that a brief exposure to AA, which either acts as a diffusible paracrine signal to OLGs or as a signal transducer, can trigger changes in protein phosphorylation in OLGs/myelin via ionic signaling events at the plasma membrane.