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Mark A Messerli

Publications and source records attributed to Mark A Messerli.

8 recordsLinked to original sources
PubMed2005

Life at acidic pH imposes an increased energetic cost for a eukaryotic acidophile.

Organisms growing in acidic environments, pH<3, would be expected to possess fundamentally different molecular structures and physiological controls in comparison with similar species restricted to neutral pH. We begin to investigate this premise by determining the magnitude of the transmembrane electrochemical H+ gradient in an acidophilic Chlamydomonas sp. (ATCC PRA-125) isolated from the Rio Tinto, a heavy metal laden, acidic river (pH 1.7-2.5). This acidophile grows most rapidly at pH 2 but is capable of growth over a wide pH range (1.5-7.0), while Chlamydomonas reinhardtii is restricted to growth at pH>or=3 with optimal growth between pH 5.5 and 8.5. With the fluorescent H+ indicator, 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF), we show that the acidophilic Chlamydomonas maintains an average cytosolic pH of 6.6 in culture medium at both pH 2 and pH 7 while Chlamydomonas reinhardtii maintains an average cytosolic pH of 7.1 in pH 7 culture medium. The transmembrane electric potential difference of Chlamydomonas sp., measured using intracellular electrodes at both pH 2 and 7, is close to 0 mV, a rare value for plants, animals and protists. The 40,000-fold difference in [H+] could be the result of either active or passive mechanisms. Evidence for active maintenance was detected by monitoring the rate of ATP consumption. At the peak, cells consume about 7% more ATP per second in medium at pH 2 than at pH 7. This increased rate of consumption is sufficient to account for removal of H+ entering the cytosol across a membrane with relatively high permeability to H+ (7x10(-8) cm s-1). Our results indicate that the small increase in the rate of ATP consumption can account for maintenance of the transmembrane H+ gradient without the imposition of cell surface H+ barriers.

Acid-Base Equilibrium↗
PubMed2004

Synergistic amplification of beta-amyloid- and interferon-gamma-induced microglial neurotoxic response by the senile plaque component chromogranin A.

Activation of the microglial neurotoxic response by components of the senile plaque plays a critical role in the pathophysiology of Alzheimer's disease (AD). Microglia induce neurodegeneration primarily by secreting nitric oxide (NO), tumor necrosis factor-alpha (TNFalpha), and hydrogen peroxide. Central to the activation of microglia is the membrane receptor CD40, which is the target of costimulators such as interferon-gamma (IFNgamma). Chromogranin A (CGA) is a recently identified endogenous component of the neurodegenerative plaques of AD and Parkinson's disease. CGA stimulates microglial secretion of NO and TNFalpha, resulting in both neuronal and microglial apoptosis. Using electrochemical recording from primary rat microglial cells in culture, we have shown in the present study that CGA alone induces a fast-initiating oxidative burst in microglia. We compared the potency of CGA with that of beta-amyloid (betaA) under identical conditions and found that CGA induces 5-7 times greater NO and TNFalpha secretion. Coapplication of CGA with betaA or with IFNgamma resulted in a synergistic effect on NO and TNFalpha secretion. CD40 expression was induced by CGA and was further increased when betaA or IFNgamma was added in combination. Tyrphostin A1 (TyrA1), which inhibits the CD40 cascade, exerted a dose-dependent inhibition of the CGA effect alone and in combination with IFNgamma and betaA. Furthermore, CGA-induced mitochondrial depolarization, which precedes microglial apoptosis, was fully blocked in the presence of TyrA1. Our results demonstrate the involvement of CGA with other components of the senile plaque and raise the possibility that a narrowly acting agent such as TyrA1 attenuates plaque formation.

Amyloid beta-Peptides↗
PubMed2004

Chloride fluxes in lily pollen tubes: a critical reevaluation.

Microelectrodes, made from a Cl(-)-selective liquid ion exchanger previously used to measure putative Cl- fluxes in Lilium longiflorum pollen tubes, were characterized. The electrodes were poorly selective, possessing only about 10-fold selectivity for Cl- over other anions tested. They had only 2.4-fold selectivity for Cl- over the anionic form of the H+ buffer, MES, indicating that the electrode can indirectly detect H+ gradients. Apparent anion influx was detected along the pollen tube shafts and at the grains while apparent anion efflux was detected near the tip of the tube. During oscillating growth, the peak of the oscillating apparent anion efflux at the tip occurred, on average, 7.9 sec after the peak of the growth oscillations. Consideration of the previously characterized H+ fluxes in lily pollen grains and tubes, as well as the poor anion selectivity of the Cl- electrodes, indicates that the putative Cl- fluxes are in fact changes in the anionic concentration of the buffer resulting from H+ gradients and not changes in Cl- concentration. The claim of a central role for Cl- in lily pollen tube growth is further undermined by the fact that these tubes grow at the same rate if the Cl- content of the growth medium is reduced to trace levels (< or =31 microM), and that the grains have only small reserves of Cl-. These results lead to the conclusion that Cl- fluxes are not a significant component of pollen tube growth and Cl- itself is not required for growth.

Anion Exchange Resins↗
PubMed2003

Ionic and osmotic disruptions of the lily pollen tube oscillator: testing proposed models.

Two mechanisms have been proposed as the primary control of oscillating tip growth in Lilium longiflorum Thunb. pollen tubes: changes in cell wall strength (Holdaway-Clarke et al. 1997) or alternatively, changes in turgor pressure (Messerli et al. 2000). Here we have modified the ionic and osmotic concentrations of the growth medium to test predictions derived from both models. Raising the [Ca2+]o tenfold above normal reduced the amplitude of the [Ca2+]i oscillations and growth oscillations while it raised the basal [Ca2+]i and growth rate such that the average growth rate did not change. Raising the [H+] of the growth medium tenfold reversibly decreased and sometimes eliminated the [Ca2+]i and growth oscillations without changing the average growth rate. Lowering the [H+] tenfold led to irregular frequency and amplitude [Ca2+]i oscillations, reduced the average growth rate of tubes and led to cell bursting in 33% of tubes. Addition of 50 mM H+ buffer, MES, to prevent pH changes in the cell wall increased the period, amplitude and duration of both [Ca2+]i and growth oscillations. Changing the [K+]o did not markedly effect [Ca2+]i oscillations. Reducing the osmolarity of the medium led to transient large-amplitude [Ca2+]i and growth oscillations while reducing large-amplitude oscillations over long periods. In many different conditions under which growth still occurs, lily pollen tubes maintain growth oscillations, albeit with modified frequency, amplitude and duration. We conclude that modifications to both proposed models are necessary to explain oscillating growth in this system.

Calcium↗
PubMed2003

Left/right, up/down: the role of endogenous electrical fields as directional signals in development, repair and invasion.

A fundamental aspect of biological systems is their spatial organization. In development, regeneration and repair, directional signals are necessary for the proper placement of the components of the organism. Likewise, pathogens that invade other organisms rely on directional signals to target vulnerable areas. It is widely understood that chemical gradients are important directional signals in living systems. Less well recognized are electrical fields, which can also provide directional information. Small, steady electrical fields can directly guide cell movement and growth and can generate chemical gradients of charged macromolecules against the leveling action of diffusion. At the site of a lesion in an ion-transporting epithelium, for example, a substantial electrical field is instantly generated and may extend over many cell diameters. There are numerous other situations in which relatively long-range electrical fields have been shown to exist naturally. Recently, there has been substantial progress in identifying specific processes that are controlled, to some extent, by these endogenous electrical fields. This review highlights these recent data and discusses possible mechanisms by which the fields might affect biological processes.

Animals↗
PubMed2003

From genes to genomes: beyond biodiversity in Spain's Rio Tinto.

Spain's Rio Tinto, or Red River, an example of an extremely acidic (pH 1.7-2.5) environment with a high metal content, teems with prokaryotic and eukaryotic microbial life. Our recent studies based on small-subunit rRNA genes reveal an unexpectedly high eukaryotic phylogenetic diversity in the river when compared to the relatively low prokaryotic diversity. Protists can therefore thrive in and dominate extremely acidic, heavy-metal-laden environments. Further, because we have discovered protistan acidophiles closely related to neutrophiles, we can hypothesize that the transition from neutral to acidic environments occurs rapidly over geological time scales. How have these organisms adapted to such environments? We are currently exploring the alterations in physiological mechanisms that might allow for growth of eukaryotic microbes at acid extremes. To this end, we are isolating phylogenetically diverse protists in order to characterize and compare ion-transporting ATPases from cultured acidophiles with those from neutrophilic counterparts. We predict that special properties of these ion transporters allow protists to survive in the Rio Tinto.

Adenosine Triphosphatases↗
PubMed2002

Pulsating ion fluxes and growth at the pollen tube tip.

Reproduction in higher plants requires the directed growth of pollen tubes in order to transmit sperm cells to the ovules at the base of the style. Many signaling processes have been implicated in polarized pollen tube growth. Here, changes in the concentration of calcium, potassium, hydrogen (pH), and chloride are discussed, as they may all contribute to the process of oscillatory growth and guidance observed in pollen tubes.

Flowers↗