Aimo Kannt
Aventis Pharma
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Publication
Featured researches published by Aimo Kannt.
Journal of Biomolecular Screening | 2004
Antje Pommereau; Everard Pap; Aimo Kannt
In this study, the authors have compared the performance of 2 high-throughput screening assays for a serin/threonine kinase: a microplate-based, bioluminescent assay that uses the luciferin/luciferase system to monitor ATP consumption, and a microfluidic assay that measures the change in mobility in an electric field of a fluorescently labeled peptide upon phosphorylation. Both assays are homogeneous, nonradioactive, antibody independent and could be miniaturized to a reaction volume of 4 μl. The robustness of both formats was demonstrated by Z′ values > 0.8. Screening of a small library (2133 compounds) showed that the results obtained with both technologies correlate very well. Although the threshold for hits was set to a comparably low value—22.2% and 13.7% inhibition for the ATP consumption and microfluidic assay, respectively, corresponding to mean plus 3 standard deviations—the overlap of active compounds identified with the 2 assay formats was greater than 94%. Thus, both assays allow the identification of even low potency inhibitors with a high level of confidence.
Nature Medicine | 2017
Weier Qi; Hillary A. Keenan; Qian Li; Atsushi Ishikado; Aimo Kannt; Thorsten Sadowski; Mark A. Yorek; I-Hsien Wu; Samuel M. Lockhart; Lawrence J. Coppey; Anja Pfenninger; Chong Wee Liew; Guifen Qiang; Alison Burkart; Stephanie M. Hastings; David M. Pober; Christopher Cahill; Monika A. Niewczas; William J. Israelsen; Liane J. Tinsley; Isaac E. Stillman; Peter S. Amenta; Edward P. Feener; Matthew G. Vander Heiden; Robert Stanton; George L. King
Diabetic nephropathy (DN) is a major cause of end-stage renal disease, and therapeutic options for preventing its progression are limited. To identify novel therapeutic strategies, we studied protective factors for DN using proteomics on glomeruli from individuals with extreme duration of diabetes (ł50 years) without DN and those with histologic signs of DN. Enzymes in the glycolytic, sorbitol, methylglyoxal and mitochondrial pathways were elevated in individuals without DN. In particular, pyruvate kinase M2 (PKM2) expression and activity were upregulated. Mechanistically, we showed that hyperglycemia and diabetes decreased PKM2 tetramer formation and activity by sulfenylation in mouse glomeruli and cultured podocytes. Pkm-knockdown immortalized mouse podocytes had higher levels of toxic glucose metabolites, mitochondrial dysfunction and apoptosis. Podocyte-specific Pkm2-knockout (KO) mice with diabetes developed worse albuminuria and glomerular pathology. Conversely, we found that pharmacological activation of PKM2 by a small-molecule PKM2 activator, TEPP-46, reversed hyperglycemia-induced elevation in toxic glucose metabolites and mitochondrial dysfunction, partially by increasing glycolytic flux and PGC-1α mRNA in cultured podocytes. In intervention studies using DBA2/J and Nos3 (eNos) KO mouse models of diabetes, TEPP-46 treatment reversed metabolic abnormalities, mitochondrial dysfunction and kidney pathology. Thus, PKM2 activation may protect against DN by increasing glucose metabolic flux, inhibiting the production of toxic glucose metabolites and inducing mitochondrial biogenesis to restore mitochondrial function.
Archive | 2004
Aimo Kannt; Antje Pommereau; Harald Thuering; Jochen Huber; Martin Oppermann
Archive | 2003
Aimo Kannt; Antje Pommereau
Archive | 2004
Norbert Tennagels; Aimo Kannt; Harald Thuering
Archive | 2006
Norbert Tennagels; Aimo Kannt; Harald Thuering
Archive | 2004
Norbert Tennagels; Aimo Kannt; Harald Thuering
Archive | 2004
Norbert Tennagels; Aimo Kannt; Harald Thuering
Archive | 2004
Aimo Kannt; Antje Pommereau
Archive | 2003
Aimo Kannt; Norbert Tennagels; Harald Thuering