Stimulation of neutral, magnesium-stimulated sphingomyelinase activity in the neurohypophysis of the rat by hypertonic saline ingestion

Guy, Norma C.; Clarke, Joe T.R.; Spence, Matthew W.; Cook, Harold W.

doi:10.1016/0361-9230(83)90028-x

Cited by 2 publications

(1 citation statement)

References 15 publications

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“…This is further supported by evidence that manumycin A, a neutral SMase inhibitor which competes with sphingomyelin for binding of neutral SMase (nSMase) (Arenz et al 2001), blocks the hypertonic inhibition of hBest1 current. In addition, the nSMase activity increases in rat neurohypophysis following hypertonic stress (Guy et al 1983). It is interesting that caveolar nSMase is activated by mechanostimulation in vascular endothelium as a mechanosensor (Czarny et al 2003; Czarny & Schnitzer, 2004).…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of human bestrophin‐1 by ceramide‐induced dephosphorylation

Xiao

Cui

et al. 2009

The Journal of Physiology

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Best vitelliform macular dystrophy is an inherited autosomal dominant, juvenile onset form of macular degeneration caused by mutations in a chloride ion channel, human bestrophin-1 (hBest1). Mutations in Best1 have also been linked to several other forms of retinopathy. In addition to mutations, hBest1 dysfunction might come about by disruption of other processes that regulate Best1 function. Here we show that hBest1 chloride channel activity is regulated by ceramide and phosphorylation. We have identified a protein kinase C (PKC) phosphorylation site (serine 358) in hBest1 that is important for sustained channel function. Channel activity is maintained by PKC activators, protein phosphatase inhibitors, or pseudo-phosphorylation by substitution of glutamic acid for serine 358. When ceramide levels are elevated by exogenous addition of ceramide to the bath, by addition of bacterial sphingomyelinase, or by hypertonic stress, S358 is rapidly dephosphorylated. The dephosphorylation is mediated by protein phosphatase 2A. Hypertonic stress-induced dephosphorylation is blocked by a dihydroceramide, an inactive form of ceramide, and manumycin, an inhibitor of neutral sphingomyelinase. Our results support a model in which ceramide accumulation during early stages of retinopathy inhibits hBest1 function, leading to abnormal fluid transport across the retina, and enhanced inflammation.

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Section: Discussionmentioning

confidence: 99%

Dysregulation of human bestrophin‐1 by ceramide‐induced dephosphorylation

Xiao

Cui

et al. 2009

The Journal of Physiology

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Interindividual heterogeneity of molecular weight of human brain neutral sphingomyelinase determined by radiation inactivation method

et al. 1986

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The molecular weight (Mr) of the membrane-bound neutral sphingomyelinase from human brain was determined using the radiation inactivation procedure. Previous studies on three human brains suggested a Mr of 165 +/- 25 kDa (J. Neurochem. 1985, 45:630-632). We now report that in another human brain the neutral sphingomyelinase had a Mr of 740 +/- 100 kDa; this higher Mr was not accompanied by differences in enzymatic properties nor heat-stability.

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Stimulation of neutral, magnesium-stimulated sphingomyelinase activity in the neurohypophysis of the rat by hypertonic saline ingestion

Cited by 2 publications

References 15 publications

Dysregulation of human bestrophin‐1 by ceramide‐induced dephosphorylation

Dysregulation of human bestrophin‐1 by ceramide‐induced dephosphorylation

Interindividual heterogeneity of molecular weight of human brain neutral sphingomyelinase determined by radiation inactivation method

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