Redox-Regulated, Targeted Affinity Isolation of NADH-Dependent Protein Interactions with the Branched Chain Aminotransferase Proteins

Author(s):  
Maya E. L. Hindy ◽  
Myra E. Conway
2011 ◽  
Vol 212 (1) ◽  
pp. 85-94 ◽  
Author(s):  
Megan N Purpera ◽  
Li Shen ◽  
Marzieh Taghavi ◽  
Heike Münzberg ◽  
Roy J Martin ◽  
...  

Elevation of dietary or brain leucine appears to suppress food intake via a mechanism involving mechanistic target of rapamycin, AMPK, and/or branched chain amino acid (BCAA) metabolism. Mice bearing a deletion of mitochondrial branched chain aminotransferase (BCATm), which is expressed in peripheral tissues (muscle) and brain glia, exhibit marked increases in circulating BCAAs. Here, we test whether this increase alters feeding behavior and brain neuropeptide expression. Circulating and brain levels of BCAAs were increased two- to four-fold in BCATm-deficient mice (KO). KO mice weighed less than controls (25.9 vs 20.4 g,P<0.01), but absolute food intake was relatively unchanged. In contrast to wild-type mice, KO mice preferred a low-BCAA diet to a control diet (P<0.05) but exhibited no change in preference for low- vs high-protein (HP) diets. KO mice also exhibited low leptin levels and increased hypothalamicNpyandAgrpmRNA. Normalization of circulating leptin levels had no effect on either food preference or the increasedNpyandAgrpmRNA expression. If BCAAs act as signals of protein status, one would expect reduced food intake, avoidance of dietary protein, and reduction in neuropeptide expression in BCATm-KO mice. Instead, these mice exhibit an increased expression of orexigenic neuropeptides and an avoidance of BCAAs but not HP. These data thus suggest that either BCAAs do not act as physiological signals of protein status or the loss of BCAA metabolism within brain glia impairs the detection of protein balance.


2002 ◽  
Vol 71 (2) ◽  
pp. 863-874 ◽  
Author(s):  
S. M. Hutson ◽  
D. Berkich ◽  
P. Drown ◽  
Baiyang Xu ◽  
Michael Aschner ◽  
...  

2012 ◽  
Vol 123 (6) ◽  
pp. 997-1009 ◽  
Author(s):  
Jonathon Hull ◽  
Maya El Hindy ◽  
Patrick G. Kehoe ◽  
Katy Chalmers ◽  
Seth Love ◽  
...  

2016 ◽  
Vol 42 (1) ◽  
pp. 306-319 ◽  
Author(s):  
Emma L. Ashby ◽  
Marta Kierzkowska ◽  
Jonathon Hull ◽  
Patrick G. Kehoe ◽  
Susan M. Hutson ◽  
...  

2011 ◽  
Vol 6 (12) ◽  
pp. 1934578X1100601 ◽  
Author(s):  
Ana Zivanovic ◽  
Natalie J. Pastro ◽  
Jane Fromont ◽  
Murray Thomson ◽  
Danielle Skropeta

The cAMP dependent protein kinase (PKA) inhibition, haemolytic activity, and cytoxicity of 21 extracts obtained from North Western Australian sponges collected from depths of 84-135 m were investigated. Hexane extracts from Ircinia/Sarcotragus sp. and Geodia sp. displayed PKA inhibitory activities of 100 and 97% respectively (at 100 μg/mL), while aq. methanol extracts from Haliclona sp. exhibited potent haemolytic activity (75%) and hexane extracts from Geodia sp. were highly toxic (88%) to the brine shrimp Artemia franciscana. As the non-polar extracts gave the greatest PKA inhibition, these were further analysed by GCMS and 29 fatty acids were identified in the highest proportions in Ircinia/Sarcotragus sp. > Haliclona sp. > Geodia sp. In contrast to shallow-water sponges that are dominated by polyunsaturated fatty acids with a high percentage of long chain fatty acids, LCFAs (C24-C30), the deep-sea sponges investigated herein were all found to be rich in saturated fatty acids, in particular C14-C20 fatty acids, including odd and branched chain fatty acids, with only low levels (0-10%) of LCFAs. Screening of the PKA inhibitory activity of a series of commercially available fatty acids identified C14-C18 fatty acids as possessing significant PKA inhibitory activity that may contribute to the activity observed in the sponges studied.


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