Contributions
Abstract: P937
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Experimental models
CPI-17 (C-kinase-activated protein phosphatase-1 (PP1) inhibitor, 17kDa) is a cytoplasmic protein predominantly expressed in mature smooth muscle cells. CPI-17 acts as a phosphorylation-dependent inhibitor protein of smooth muscle myosin phosphatase. Myosin phosphatase inhibition increases myosin phosphorylation and in consequence smooth muscle contraction in the absence of increased intracellular Ca2+ concentrations. One factor regulating CPI-17 activity via phosphorylation is Protein kinase C (PKC). Since phosphorylation states are integral for oligodendrocyte proliferation and differentiation, in this project, we aimed at identifying new regulatory proteins involved in remyelination.
In a first step, genome-wide array analyses were performed to screen for potential candidate proteins regulating oligodendrocyte stability. We used the cuprizone model since in this model early oligodendrocyte apoptosis is paralleled by a selective and massive reduction of oligodendrocyte specific mRNA species. After 2 days of cuprizone intoxication, the expression of various proteins was profoundly decreased, among CPI-17. Immunohistochemical studies showed that CPI-17 is exclusively expressed in mature oligodendrocytes. CPI-17 expressing cells are lost under various demyelinating conditions including the cuprizone model, focal lysophosphatidylcholine (LPC) injection into the brain or experimental autoimmune encephalomyelitis (EAE). CPI-17 expressing oligodendrocytes are as well lost in active and chronic Multiple sclerosis (MS) lesions. Furthermore, CPI-17 deficient animals show impaired remyelination and augmented acute axonal damage after cuprizone-induced demyelination compared to wild type littermates.
In this study, we identified a novel regulator of oligodendrocyte differentiation. Future studies are now needed to understand how CPI-17 regulates remyelination.
Disclosure: This study was supported by the Robert Pfleger Stiftung.
Abstract: P937
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Experimental models
CPI-17 (C-kinase-activated protein phosphatase-1 (PP1) inhibitor, 17kDa) is a cytoplasmic protein predominantly expressed in mature smooth muscle cells. CPI-17 acts as a phosphorylation-dependent inhibitor protein of smooth muscle myosin phosphatase. Myosin phosphatase inhibition increases myosin phosphorylation and in consequence smooth muscle contraction in the absence of increased intracellular Ca2+ concentrations. One factor regulating CPI-17 activity via phosphorylation is Protein kinase C (PKC). Since phosphorylation states are integral for oligodendrocyte proliferation and differentiation, in this project, we aimed at identifying new regulatory proteins involved in remyelination.
In a first step, genome-wide array analyses were performed to screen for potential candidate proteins regulating oligodendrocyte stability. We used the cuprizone model since in this model early oligodendrocyte apoptosis is paralleled by a selective and massive reduction of oligodendrocyte specific mRNA species. After 2 days of cuprizone intoxication, the expression of various proteins was profoundly decreased, among CPI-17. Immunohistochemical studies showed that CPI-17 is exclusively expressed in mature oligodendrocytes. CPI-17 expressing cells are lost under various demyelinating conditions including the cuprizone model, focal lysophosphatidylcholine (LPC) injection into the brain or experimental autoimmune encephalomyelitis (EAE). CPI-17 expressing oligodendrocytes are as well lost in active and chronic Multiple sclerosis (MS) lesions. Furthermore, CPI-17 deficient animals show impaired remyelination and augmented acute axonal damage after cuprizone-induced demyelination compared to wild type littermates.
In this study, we identified a novel regulator of oligodendrocyte differentiation. Future studies are now needed to understand how CPI-17 regulates remyelination.
Disclosure: This study was supported by the Robert Pfleger Stiftung.