1.Brain interstitial fluid glutamine homeostasis is controlled by blood-brain barrier SLC7A5/LAT1 amino acid transporter.
Dolgodilina E1, Imobersteg S2, Laczko E3, Welt T2, Verrey F4, Makrides V1. J Cereb Blood Flow Metab. 2015 Oct 19. pii: 0271678X15609331. [Epub ahead of print]
L-glutamine (Gln) is the most abundant amino acid in plasma and cerebrospinal fluid and a precursor for the main central nervous system excitatory (L-glutamate) and inhibitory (γ-aminobutyric acid (GABA)) neurotransmitters. Concentrations of Gln and 13 other brain interstitial fluid amino acids were measured in awake, freely moving mice by hippocampal microdialysis using an extrapolation to zero flow rate method. Interstitial fluid levels for all amino acids including Gln were ∼5-10 times lower than in cerebrospinal fluid. Although the large increase in plasma Gln by intraperitoneal (IP) injection of 15N2-labeled Gln (hGln) did not increase total interstitial fluid Gln, low levels of hGln were detected in microdialysis samples. Competitive inhibition of system A (SLC38A1&2; SNAT1&2) or system L (SLC7A5&8; LAT1&2) transporters in brain by perfusion with α-(methylamino)-isobutyric acid (MeAIB) or 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) respectively, was tested.
2.Helical peptide-polyamine and -polyether conjugates as synthetic ionophores.
Benincasa M1, Francescon M2, Fregonese M2, Gennaro R3, Pengo P2, Rossi P2, Scrimin P4, Tecilla P5. Bioorg Med Chem. 2015 Dec 1;23(23):7386-93. doi: 10.1016/j.bmc.2015.10.034. Epub 2015 Oct 24.
Two new synthetic ionophores in which the hydrophobic portion is represented by a short helical Aib-peptide (Aib=α-amino-isobutyric acid) and the hydrophilic one is a poly-amino (1a) or a polyether (1b) chain have been prepared. The two conjugates show a high ionophoric activity in phospholipid membranes being able to efficiently dissipate a pH gradient and, in the case of 1b, to transport Na(+) across the membrane. Bioactivity evaluation of the two conjugates shows that 1a has a moderate antimicrobial activity against a broad spectrum of microorganisms and it is able to permeabilize the inner and the outer membrane of Escherichia coli cells.
3.An ethylene and ROS-dependent pathway is involved in low ammonium-induced root hair elongation in Arabidopsis seedlings.
Zhu C1, Yang N1, Guo Z1, Qian M1, Gan L2. Plant Physiol Biochem. 2016 Apr 2;105:37-44. doi: 10.1016/j.plaphy.2016.04.002. [Epub ahead of print]
Root hairs are plastic in response to nutrient supply, but relatively little is known about their development under low ammonium (NH4+) conditions. This study showed that reducing NH4+ for 3 days in wild-type Arabidopsis seedlings resulted in drastic elongation of root hairs. To investigate the possible mediation of ethylene and auxin in this process, seedlings were treated with 2,3,5-triiodobenzoic acid (TIBA, auxin transport inhibitor), 1-naphthylphthalamic acid (NPA, auxin transport inhibitor), p-chlorophenoxy isobutyric acid (PCIB, auxin action inhibitor), aminoethoxyvinylglycine (AVG, chemical inhibitor of ethylene biosynthesis), or silver ions (Ag+, ethylene perception antagonist) under low NH4+ conditions. Our results showed that TIBA, NPA and PCIB did not inhibit root hair elongation under low NH4+ conditions, while AVG and Ag+ completely inhibited low NH4+-induced root hair elongation. This suggested that low NH4+-induced root hair elongation was dependent on the ethylene pathway, but not the auxin pathway.
4.In-vivo imaging of blood-brain barrier permeability using positron emission tomography with 2-amino-[3-11C]isobutyric acid.
Okada M1, Kikuchi T, Okamura T, Ikoma Y, Tsuji AB, Wakizaka H, Kamakura T, Aoki I, Zhang MR, Kato K. Nucl Med Commun. 2015 Dec;36(12):1239-48. doi: 10.1097/MNM.0000000000000385.
OBJECTIVE: The blood-brain barrier (BBB) limits the entry of some therapeutics into the brain, resulting in reduced efficacy. BBB-opening techniques have been developed to enhance the entry into the brain. However, a noninvasive, highly sensitive and quantitative method for evaluating the changes in BBB permeability induced by such techniques is needed to optimize treatment protocols. We evaluated 2-amino-[3-C]isobutyric acid ([3-C]AIB) as a PET probe to quantify BBB permeability in model rats.
