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Träfflista för sökning "L773:0027 8424 OR L773:1091 6490 ;pers:(Uhlen P)"

Sökning: L773:0027 8424 OR L773:1091 6490 > Uhlen P

  • Resultat 1-4 av 4
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1.
  • Aizman, O., et al. (författare)
  • Ouabain, a steroid hormone that signals with slow calcium oscillations
  • 2001
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 98:23, s. 13420-13424
  • Tidskriftsartikel (refereegranskat)abstract
    • The plant-derived steroid, digoxin, a specific inhibitor of Na,K-ATPase, has been used for centuries in the treatment of heart disease. Recent studies demonstrate the presence of a digoxin analog, ouabain, in mammalian tissue, but its biological role has not been elucidated. Here, we show in renal epithelial cells that ouabain, in doses causing only partial Na,K-ATPase inhibition, acts as a biological inducer of regular, low-frequency intracellular calcium ([Ca2+](i)) oscillations that elicit activation of the transcription factor, NF-KB. Partial inhibition of Na,K-ATPase using low extracellular K+ and depolarization of cells did not have these effects. Incubation of cells in Ca2+-free media, inhibition of voltage-gated calcium channels, inositol triphosphate receptor antagonism, and redistribution of actin to a thick layer adjacent to the plasma membrane abolished [Ca2+](i) oscillations, indicating that they were caused by a concerted action of inositol triphosphate receptors and capacitative calcium entry via plasma membrane channels. Blockade of ouabain-induced [C-a2+](i) oscillations prevented activation of NF-kappaB. The results demonstrate a new mechanism for steroid signaling via plasma membrane receptors and underline a novel role for the steroid hormone, ouabain, as a physiological inducer of [Ca2+](i) oscillations involved in transcriptional regulation in mammalian cells.
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2.
  • Bernard-Marissal, N, et al. (författare)
  • Altered interplay between endoplasmic reticulum and mitochondria in Charcot-Marie-Tooth type 2A neuropathy
  • 2019
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 116:6, s. 2328-2337
  • Tidskriftsartikel (refereegranskat)abstract
    • Interactions between mitochondria and the endoplasmic reticulum (ER) at the level of mitochondria-associated membranes (MAM) constitute a key signaling hub, emerging as a shared target altered in multiple neurodegenerative diseases. We use both in vivo and in vitro models of Charcot–Marie–Tooth type 2A, an axonal form of neuropathy, to demonstrate that the presence of mutated Mitofusin 2 leads to altered MAM. In neurons, these modifications occur concomitantly with activation of ER stress response, dysregulated calcium handling, and alterations in mitochondrial morphology and transport, collectively contributing to axonopathy. Importantly, the reported results indicate that the pathological consequences of mutated Mitofusin 2 may be targeted with drugs reinforcing the ER–mitochondria cross-talk and/or reducing ER stress.
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3.
  • Eklof-Ljunggren, E, et al. (författare)
  • Origin of excitation underlying locomotion in the spinal circuit of zebrafish
  • 2012
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 109:14, s. 5511-5516
  • Tidskriftsartikel (refereegranskat)abstract
    • Neural circuits in the spinal cord transform instructive signals from the brain into well-coordinated locomotor movements by virtue of rhythm-generating components. Although evidence suggests that excitatory interneurons are the essence of locomotor rhythm generation, their molecular identity and the assessment of their necessity have remained unclear. Here we show, using larval zebrafish, that V2a interneurons represent an intrinsic source of excitation necessary for the normal expression of the locomotor rhythm. Acute and selective ablation of these interneurons increases the threshold of induction of swimming activity, decreases the burst frequency, and alters the coordination of the rostro–caudal propagation of activity. Thus, our results argue that V2a interneurons represent a source of excitation that endows the spinal circuit with the capacity to generate locomotion.
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4.
  • Lee, MD, et al. (författare)
  • Small-world connectivity dictates collective endothelial cell signaling
  • 2022
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 119:18, s. e2118927119-
  • Tidskriftsartikel (refereegranskat)abstract
    • The endothelium is the single layer of cells lining all blood vessels and acts as a central control hub to regulate multiple cardiovascular functions in response to hundreds of physiological stimuli. The detection of various physiological stimuli is distributed in spatially separated sites across the endothelium. Distributed sensing is difficult to reconcile with the requirement for coordinated cell activity across large regions of the endothelium. Here, we show that the endothelium resolves the issue by using a network with scale-free and small-world properties. The organization confers a high signal-propagation speed and a high degree of synchronizability across the endothelium. The network organization also explains the robust nature of endothelial communication and its resistance to damage or failure.
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  • Resultat 1-4 av 4

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