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- Jansen-Olesen, I, et al.
(författare)
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Expression of inducible nitric oxide synthase in trigeminal ganglion cells during culture
- 2005
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - 1742-7843. ; 97:6, s. 355-363
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Tidskriftsartikel (refereegranskat)abstract
- Nitric oxide (NO) is an important signalling molecule that has been suggested to be a key molecule for induction and maintenance of migraine attacks based on clinical studies, animal experimental studies and the expression of nitric oxide synthase (NOS) immuno reactivity within the trigeminovascular system. Sensitisation of the trigeminal system including the trigeminal ganglia neurones is believed to be involved in the pathway leading to migraine pain. In the present study, the NOS expression in rat primary trigeminal ganglia neurones was examined at different time points using immuno-cytochemistry, reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting. In trigeminal ganglia cells not subjected to culture, endothelial (e) and neuronal (n) but not inducible (i) NOS mRNA and protein were detected. Culture of rat neurotics resulted in a rapid axonal Outgrowth of NOS positive fibres. At 12, 24 and 48 hr of culture, NOS immunoreactivity was detected in medium-sized trigeminal ganglia cells. Western blotting and RT-PCR revealed an up-regulation of inducible iNOS expression during Culture. However, after Culture only low levels of eNOS protein was found while no eNOS and nNOS mRNA and protein could be detected. The data Suggest that iNOS expression may be a molecular mechanism mediating the adaptive response of trigeminal ganglia cells to the serum free stressful stimulus the Culture environment provides. It may act as a cellular signalling molecule that is expressed after cell activation.
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| 2. |
- Kristensen, Kristian K., et al.
(författare)
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Unfolding of monomeric lipoprotein lipase by ANGPTL4 : Insight into the regulation of plasma triglyceride metabolism
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:8, s. 4337-4346
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Tidskriftsartikel (refereegranskat)abstract
- The binding of lipoprotein lipase (LPL) to GPIHBP1 focuses the intravascular hydrolysis of triglyceride-rich lipoproteins on the surface of capillary endothelial cells. This process provides essential lipid nutrients for vital tissues (e.g., heart, skeletal muscle, and adipose tissue). Deficiencies in either LPL or GPIHBP1 impair triglyceride hydrolysis, resulting in severe hypertriglyceridemia. The activity of LPL in tissues is regulated by angiopoietin-like proteins 3, 4, and 8 (ANGPTL). Dogma has held that these ANGPTLs inactivate LPL by converting LPL homodimers into monomers, rendering them highly susceptible to spontaneous unfolding and loss of enzymatic activity. Here, we show that binding of an LPL-specific monoclonal antibody (5D2) to the tryptophan-rich lipid-binding loop in the carboxyl terminus of LPL prevents homodimer formation and forces LPL into a monomeric state. Of note, 5D2-bound LPL monomers are as stable as LPL homodimers (i.e., they are not more prone to unfolding), but they remain highly susceptible to ANGPTL4-catalyzed unfolding and inactivation. Binding of GPIHBP1 to LPL alone or to 5D2-bound LPL counteracts ANGPTL4-mediated unfolding of LPL. In conclusion, ANGPTL4-mediated inactivation of LPL, accomplished by catalyzing the unfolding of LPL, does not require the conversion of LPL homodimers into monomers. Thus, our findings necessitate changes to long-standing dogma on mechanisms for LPL inactivation by ANGPTL proteins. At the same time, our findings align well with insights into LPL function from the recent crystal structure of the LPL•GPIHBP1 complex.
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