Characterization and localization of mitochondrial oligopeptidase (MOP) (EC 3.4.24.16) activity in the human cervical adenocarcinoma cell line HeLa

Krause, Darren; Piva, Terrence J.; Brown, S. B.; Ellem, K.A.O.

doi:10.1002/(sici)1097-4644(19970901)66:3<297::aid-jcb3>3.0.co;2-k

Cited by 14 publications

(9 citation statements)

References 45 publications

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“…Also many studies using shRNA or chemical inhibitors supported the involvement of Nln in these physiological processes (24,28,78). Even though Nln is expressed widely in the central nervous system and peripheral organs of mammals (13,83,84), its absence, as shown here, is not lethal. KO mice reproduce normally and have normal blood pressure and heart rate when compared with WT mice.…”

Section: Ms Spectrasupporting

confidence: 62%

Neurolysin Knockout Mice Generation and Initial Phenotype Characterization

Cavalcanti¹,

Castro

Neto³

et al. 2014

Journal of Biological Chemistry

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Background:Neurolysin is known to cleave several bioactive peptides in vitro. Results: Neurolysin knock-out mice showed increased glucose tolerance, insulin sensitivity, and gluconeogenesis, which likely relates to increased expression of both specific liver mRNAs and intracellular peptides. Conclusion: Neurolysin plays a role in energy metabolism. Significance: Neurolysin could be used as a therapeutic target to counteract insulin resistance.The oligopeptidase neurolysin (EC 3.4.24.16; Nln) was first identified in rat brain synaptic membranes and shown to ubiquitously participate in the catabolism of bioactive peptides such as neurotensin and bradykinin. Recently, it was suggested that Nln reduction could improve insulin sensitivity. Here, we have shown that Nln KO mice have increased glucose tolerance, insulin sensitivity, and gluconeogenesis. KO mice have increased liver mRNA for several genes related to gluconeogenesis. Isotopic label semiquantitative peptidomic analysis suggests an increase in specific intracellular peptides in gastrocnemius and epididymal adipose tissue, which likely is involved with the increased glucose tolerance and insulin sensitivity in the KO mice. These results suggest the exciting new possibility that Nln is a key enzyme for energy metabolism and could be a novel therapeutic target to improve glucose uptake and insulin sensitivity.

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Section: Ms Spectrasupporting

confidence: 62%

Neurolysin Knockout Mice Generation and Initial Phenotype Characterization

Cavalcanti¹,

Castro

Neto³

et al. 2014

Journal of Biological Chemistry

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“…Of note, there is one report claiming that human neurolysin does not metabolize somatostatin [31]. Orexin B, which is also reported to be a substrate of neurolysin [29] displayed a slightly greater inhibition of 125 I-SI Ang II binding, 31 and 41% in brain and testis, respectively.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological characterization of a novel non-AT1, non-AT2 angiotensin binding site identified as neurolysin

2013

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The discovery of a novel non-AT1, non-AT2 binding site for angiotensins in the rodent brain and testis that is unmasked by the organomercurial compound para-chloromercuribenzoic acid (PCMB) has catalyzed efforts to purify and characterize this protein. We recently reported that this protein is neurolysin and now report upon the specificity of this binding site for various neuropeptides. Competition binding assays in rat brain and testis used 125I-Sar1, Ile8 angiotensin II (Ang II) as the radioligand in the presence of saturating concentrations of AT1 and AT2 receptor antagonists and 100 µM parachloromercuribenzoate. Primary screening of 36 peptides and other compounds at 10 µM concentration revealed seven peptides that inhibited specific binding > 50%: ghrelin, Tyr1 S36057 (a melanin-concentrating hormone receptor ligand), orphanin FQ and its congeners (Tyr1 and Tyr14), Dynorphin A (1–8), and Ang (1–9). The selective neurolysin inhibitor Proline-Isoleucine dipeptide was inactive at 1 mM. These results suggest that the ability of PCMB to unmask high affinity binding of Ang II to neurolysin is a pharmacological effect and that neurolysin may significantly affect the activity of the reninangiotensin system.

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“…Mitochondria were isolated from cultured TM cells, corneal fibroblasts, or mouse liver using techniques adapted from previously reported, well‐established methods (Krause et al, 1997; Cavadini et al, 2002; Kaufmann et al, 2003). Cells or tissues were homogenized in homogenization buffer (HB) containing 220 mM mannitol, 70 mM sucrose, 10 mM HEPES, pH 7.4, 1 mM EDTA, 1 mM EGTA, 0.5% bovine serum albumin, and protease inhibitors.…”

Section: Methodsmentioning

confidence: 99%

An extensive study on automated Dewey Decimal Classification

Wang

2009

J. Am. Soc. Inf. Sci.

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In this paper, we present a theoretical analysis and extensive experiments on the automated assignment of Dewey Decimal Classification (DDC) classes to bibliographic data with a supervised machine-learning approach. Library classification systems, such as the DDC, impose great obstacles on state-of-art text categorization (TC) technologies, including deep hierarchy, data sparseness, and skewed distribution. We first analyze statistically the document and category distributions over the DDC, and discuss the obstacles imposed by bibliographic corpora and library classification schemes on TC technology. To overcome these obstacles, we propose an innovative algorithm to reshape the DDC structure into a balanced virtual tree by balancing the category distribution and flattening the hierarchy. To improve the classification effectiveness to a level acceptable to real-world applications, we propose an interactive classification model that is able to predict a class of any depth within a limited number of user interactions. The experiments are conducted on a large bibliographic collection created by the Library of Congress within the science and technology domains over 10 years. With no more than three interactions, a classification accuracy of nearly 90% is achieved, thus providing a practical solution to the automatic bibliographic classification problem.

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Characterization and localization of mitochondrial oligopeptidase (MOP) (EC 3.4.24.16) activity in the human cervical adenocarcinoma cell line HeLa

Cited by 14 publications

References 45 publications

Neurolysin Knockout Mice Generation and Initial Phenotype Characterization

Neurolysin Knockout Mice Generation and Initial Phenotype Characterization

Pharmacological characterization of a novel non-AT1, non-AT2 angiotensin binding site identified as neurolysin

An extensive study on automated Dewey Decimal Classification

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