Browsing by Subject "peptides"

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    Brain natriuretic peptide suppresses pain induced by BmK I, a sodium channel-specific modulator, in rats.
    (Springer, 2016) Li, Zheng-Wei; Wu, Bin; Ye, Pin; Tan, Zhi-Yong; Ji, Yong-Hua; Department of Pharmacology and Toxicology, IU School of Medicine
    Background: A previous study found that brain natriuretic peptide (BNP) inhibited inflammatory pain via activating its receptor natriuretic peptide receptor A (NPRA) in nociceptive sensory neurons. A recent study found that functional NPRA is expressed in almost all the trigeminal ganglion (TG) neurons at membrane level suggesting a potentially important role for BNP in migraine pathophysiology. Methods: An inflammatory pain model was produced by subcutaneous injection of BmK I, a sodium channel-specific modulator from venom of Chinese scorpion Buthus martensi Karsch. Quantitative PCR, Western Blot, and immunohistochemistry were used to detect mRNA and protein expression of BNP and NPRA in dorsal root ganglion (DRG) and dorsal horn of spinal cord. Whole-cell patch clamping experiments were conducted to record large-conductance Ca2+-activated K+ (BKCa) currents of membrane excitability of DRG neurons. Spontaneous and evoked pain behaviors were examined. Results: The mRNA and protein expression of BNP and NPRA was up-regulated in DRG and dorsal horn of spinal cord after BmK I injection. The BNP and NPRA was preferentially expressed in small-sized DRG neurons among which BNP was expressed in both CGRP-positive and IB4-positive neurons while NPRA was preferentially expressed in CGRP-positive neurons. BNP increased the open probability of BKCa channels and suppressed the membrane excitability of small-sized DRG neurons. Intrathecal injection of BNP significantly inhibited BmK-induced pain behaviors including both spontaneous and evoked pain behaviors. Conclusions: These results suggested that BNP might play an important role as an endogenous pain reliever in BmK I-induced inflammatory pain condition. It is also suggested that BNP might play a similar role in other pathophysiological pain conditions including migraine.
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    Identifying Potential Proteasomal assembly factors and/or binding proteins using the yeast Saccharomyces cerevisiae as a model organism
    (Office of the Vice Chancellor for Research, 2015-04-17) Lindsay, Nicole; Hammack, Lindsay; Kusmiercyzk, Andrew
    The proteasome is a large multi-protein complex responsible for the ultimate degradation of proteins in the cell. Damaged or misfolded proteins are targeted for destruction and broken down into peptides. Proteasomal degradation plays a vital role in almost every cellular process, from the cell cycle, to cell development, to apoptosis. Moreover, understanding and identifying the proteasome assembly process, important binding factors, and chaperones that assist in proteasome assembly would be pivotal in developing strategies to remedy cellular disorders caused by defects in proteasomal function. The eukaryotic proteasome is composed of two main sub-complexes, a 20S core particle and a 19S regulatory particle that caps one or both ends of the 20S core particle. The 20S core particle is the degradation component of the proteasome, and it is made up of 14 unique subunits with seven distinct α and β subunits that assemble into four stacked heteroheptameric rings. On the β7 subunit, there is a C-terminal peptide tail that connects two halves of the 20S core particle. Previous research has shown that deletion of the β7 tail slows down proteasome assembly. We generated a yeast strain containing a deletion of the β7 tail along with deletion of two assembly factors, Pba1p and Ump1p. This strain is severely temperature sensitive and will be used to screen a plasmid-borne yeast genomic library. The goal is to potentially identify new proteasomal chaperones and/or binding partners which, when present in high copy, can overcome the defect imposed by the triple mutant.