Interactions between carnosine and zinc and copper: implications for neuromodulation and neuroprotection

This review examines interactions in the mammalian central nervous system (CNS) between carnosine and the endogenous transition metals zinc and copper. Although the relationship between these substances may be applicable to other brain regions, the focus is on the olfactory system where these substances may have special significance. Carnosine is not only highly concentrated in the olfactory system, but it is also contained in neurons (in contrast to glia cells in most of the brain) and has many features of a neurotransmitter. Whereas the function of carnosine in the CNS is not well understood, we review evidence that suggests that it may act as both a neuromodulator and a neuroprotective agent. Although zinc and/or copper are found in many neuronal pathways in the brain, the concentrations of zinc and copper in the olfactory bulb (the target of afferent input from sensory neurons in the nose) are among the highest in the CNS. Included in the multitude of physiological roles that zinc and copper play in the CNS is modulation of neuronal excitability. However, zinc and copper also have been implicated in a variety of neurologic conditions including Alzheimer's disease, Parkinson's disease, stroke, and seizures. Here we review the modulatory effects that carnosine can have on zinc and copper's abilities to influence neuronal excitability and to exert neurotoxic effects in the olfactory system. Other aspects of carnosine in the CNS are reviewed elsewhere in this issue.     

The use of a hybrid linear trap/FT-ICR mass spectrometer for on-line high resolution/high mass accuracy bottom-up sequencing.

In this work we present a hybrid linear trap/Fourier transform ion cyclotron resonance (ICR) mass spectrometer to perform protein sequencing using the bottom-up approach. We demonstrate that incorporation of the linear trap greatly enhances the overall performance of the hybrid system for the study of complex peptide mixtures separated by fast high-performance liquid chromatography gradients. The ability to detect in the linear trap enables employment of automatic gain control to greatly reduce space charging in the ICR cell irregardless of ion flux. Resulting accurate mass measurements of 2 ppm or better using external calibration are achieved for the base peak as well as ions at 2% relative abundance. The linear trap is used to perform ion accumulation and activation prior to detection in the ICR cell which increases the scan rate. The increased duty cycle allows for data-dependent mass analysis of coeluting peptides to be acquired increasing protein sequence coverage without increasing the gradient length. In addition, the linear trap could be used as an ion detection device to perform simultaneous detection of tandem mass spectra with full scan mass spectral detection in the ICR cell resulting in the fastest scan cycles for performing bottom-up sequencing of protein digests. Comparisons of protein sequence coverage are presented for product ion detection in the linear trap and ICR cell.     

Small Molecule Modifiers of In Vitro Manganese Transport Alter Toxicity In Vivo

Biological Trace Element Research - Manganese (Mn) is essential for several species and daily requirements are commonly met by an adequate diet. Mn overload may cause motor and psychiatric...     

DEVELOPMENT OF HEMOGLOBIN, HEMATOCRIT, AND ERYTHROCYTE VALUES IN GALÁPAGOS FUR SEALS

We studied the ontogeny of hemoglobin concentration, hematocrit and erythrocyte counts in the Galapagos fur seal ( Arctocephalus galapagoensis , Heller 1904). Two hundred and fifty-three animals were sampled between the ages of 22 d and > 8 yr, of which 46 were adult females. Body mass increased steadily with age from 6.1 ± 1.2 kg in 1-mo-old pups ( n = 27) to 28.5 ± 3.3 kg in adult females. Even adult females increased in mass with age. Hemoglobin (Hb), hematocrit (Hct), and red blood cell (RBC) values all increased in a logarithmic fashion with age up to 2 yr. Blood values for pups were Hct: 35.5 ± 4.1%; Hb: 12.9 ± 1.3 g/dl; RBC: 4.1 ± 0.3·10⁶/μl. Half-year-old fur seals (Hct: 42.1 ± 3.2%; Hb: 15.7 ± 1.3 g/dl; RBC: 4.9 ± 0.5·10⁶/μl; n = 50) were the oldest age group to show significantly lower blood values than adult females ( P < 0.001 for all three parameters). Yearling blood values (Hct: 47.2 ± 3.6%; Hb: 17.3 ± 1.6 g/dl; RBC: 5.6 ± 0.4·10⁶/μl; n = 56) did not differ significantly from those of adult females ( P < 0.32; P < 0.26; P < 0.23, respectively). Blood values of adult females were lower than those of 2-yr-olds (Hct: 49.6 ± 2.4%; Hb: 18.5 ± 1.2 g/dl; RBC: 5.7 ± 0.3·10⁶/μl; n = 31). These differences were significant only for RBCs ( P < 0.003). Up to the age of 1 yr, age was the best predictor for blood values, thereafter mass tended to be a better predictor. Female juveniles between the ages of 150 and 600 d had higher blood values than same-age males. The relationship of blood value development to diving activity is briefly described and the results are compared to values of other marine mammals. Ontogeny is discussed in relation to the development of these blood values in terrestrial mammals.     

Autoregulation of glucose production in men with a glycerol load during rest and exercise

Related to hepatic autoregulation we evaluated hypotheses that 1) glucose production would be altered as a result of a glycerol load, 2) decreased glucose recycling rate (Rr) would result from increased glycerol uptake, and 3) the absolute rate of gluconeogenesis (GNG) from glycerol would be positively correlated to glycerol rate of disappearance (R(d)) during a glycerol load. For these purposes, glucose and glycerol kinetics were determined in eight men during rest and during 90 min of leg cycle ergometry at 45 and 65% of peak O2 consumption (.VO2 (peak)). Trials were conducted after an overnight fast, with exercise commencing 12 h after the last meal. Subjects received a continuous infusion of [6,6-(2)H(2)]glucose, [1-(13)C]glucose, and [1,1,2,3,3-(2)H(5)]glycerol without (CON) or with an additional 1,000 mg (rest: 20 mg/min; exercise: 40 mg/min) of [2-(13)C]- or unlabeled glycerol added to the infusate (GLY). Infusion of glycerol dampened glucose Rr, calculated as the difference between [6,6-(2)H(2)]- and [1-(13)C]glucose rates of appearance (R(a)), at rest [0.35 +/- 0.12 (CON) vs. 0.12 +/- 0.10 mg. kg(-1). min(-1) (GLY), P < 0.05] and during exercise at both intensities [45%: 0.63 +/- 0.14 (CON) vs. 0.04 +/- 0.12 (GLY); 65%: 0.73 +/- 0.14 (CON) vs. 0.04 +/- 0.17 mg. kg(-1). min(-1) (GLY), P < 0.05]. Glucose R(a) and oxidation were not affected by glycerol infusion at rest or during exercise. Throughout rest and both exercise intensities, glycerol R(d) was greater in GLY vs. CON conditions (rest: 0.30 +/- 0.04 vs. 0.58 +/- 0.04; 45%: 0.57 +/- 0.07 vs. 1.19 +/- 0.04; 65%: 0.73 +/- 0.06 vs. 1.27 +/- 0.05 mg. kg(-1). min(-1), CON vs. GLY, respectively). Differences in glycerol R(d) (DeltaR(d)) between protocols equaled the unlabeled glycerol infusion rate and correlated with plasma glycerol concentration (r = 0.97). We conclude that infusion of a glycerol load during rest and exercise at 45 and 65% of .VO2(peak) 1) does not affect glucose R(a) or R(d), 2) blocks glucose Rr, 3) increases whole body glycerol R(d) in a dose-dependent manner, and 4) results in gluconeogenic rates from glycerol equivalent to CON glucose recycling rates.