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M B Djamgoz

Publications and source records attributed to M B Djamgoz.

At least 19 recordsLinked to original sources
PubMed2001

Structure-function correlation in transient amacrine cells of goldfish retina: basic and multifractal analyses of dendritic trees in distinct synaptic layers.

Amacrine cells generating light-evoked transient ON-OFF responses were stained by intracellular injection of horseradish peroxidase after determining their input-output (voltage response vs. light intensity) profiles. Ten cells specifically having bistratified dendritic trees were analyzed. The cross-sectional area of the dendrites in each sublamina (a and b) of the inner plexiform layer was initially measured. Although some variability was observed, there was no statistically significant overall difference in the cross-sectional areas of the dendritic trees in sublaminae a and b. Also, the amplitudes of the ON and OFF responses, generated by a midrange criterion stimulus, could not be correlated with the cross-sectional areas or the number of branches of the dendrites in sublaminae b and a, respectively. On the other hand, determination of the generalized fractal spectra revealed that the negative (up to -3) and zero-order fractal dimensions of the dendritic trees in sublamina a were consistently higher than those for sublamina b. Furthermore, there was a positive correlation between response amplitude and some part of the generalized fractal dimension in the respective parts of the dendritic trees. It is concluded that dendritic tree characteristics differ in the two halves of the inner plexiform layer and that these can be related to the cells' light-evoked response amplitudes. Furthermore, generalized fractal analysis appears to be a useful method for correlating structure and function in retinal amacrine cells with complex dendritic trees.

Algorithms↗
PubMed2001

Expression profiles of voltage-gated Na(+) channel alpha-subunit genes in rat and human prostate cancer cell lines.

BACKGROUND: Voltage-gated Na(+) channel (VGSC) activity has been implicated in prostate cancer (PC) metastasis. Although VGSCs can occur as multiple-subunit assemblies, the alpha-subunits (VGSCalphas) alone can encode functional channels. The VGSCalpha gene(s) responsible for the functional VGSCalpha expression in strongly metastatic PC cell lines is not known. METHODS: Two reverse transcription-PCR (RT-PCR) methods, degenerate primer screening and a novel semi quantitative PCR (SQT-PCR) technique, were used. These methods enabled a detailed qualitative and quantitative investigation of VGSCalpha mRNA expression in rat (MAT-LyLu/AT-2) and human (PC-3/LNCaP) PC cells of markedly different metastatic potential. RESULTS: Expression of eight different VGSCalpha genes (SCN1A-4A, SCN7A-9A, and SCN11A) was determined in the PC cell lines. Most were expressed as multiple splice variants. SQT-PCR results were consistent with a basal level of VGSCalpha mRNA expression occurring in weakly metastatic (AT-2/LNCaP) cells, and this being greatly elevated in cells of stronger metastatic potential (MAT-LyLu/PC-3), primarily due to the elevated expression of the SCN9A gene (also termed PN1/hNe-Na). CONCLUSIONS: (1) Several VGSCalpha genes and their splice variants are expressed similarly in both rat and human PC cell lines. (2) Expression levels are much higher in the strongly metastatic (MAT-LyLu/PC-3) cells. (3) Levels of SCN9A mRNA specifically are predominant in MAT-LyLu and PC-3 cells; thus, SCN9A is highly likely to be the main source of the functional VGSC detected.

Animals↗
PubMed2001

An electrophysiological test of the effect of the temporal pattern of light adaptation on teleost H1 type horizontal cell plasticity.

The possible importance of the temporal pattern of photon delivery in light adaptation-induced physiological plasticity in the outer retina of carp was tested by intracellular recording. Steady and flicker (3 Hz) background adaptation was applied whilst recording chromatic voltage responses of H1 type horizontal cells (HCs) to 680 and 440 nm full-field test flashes (generating response amplitudes of V(r) and V(b), respectively). A third parameter V(b)/V(r) (B/R) was calculated as an indicator of the cells' short/long wavelength relative spectral contrast. Steady light adaptation increased V(r) and to a lesser extent V(b), and reduced B/R. Flicker adaptation also increased V(r) (by a similar amount), but, unlike steady adaptation, consistently decreased V(b). The reduction in B/R was statistically greater for flicker than for steady adaptation, although the former delivered half as many photons to the retina. These results suggest that the temporal pattern of light adaptation is indeed an important determinant of qualitative and quantitative aspects of plasticity induced in the outer retina, and complement earlier morphological findings. The effects are discussed in terms of dopamine and nitric oxide as underlying possible neurochemical control mechanisms.

Adaptation, Ocular↗
PubMed2001

Nerve growth factor induces light adaptive cellular and synaptic plasticity in the outer retina of fish.

Recent evidence suggests that neurotrophins can be involved in short-term synaptic plasticity in parts of the central nervous system. In the present study, the possible role of nerve growth factor (NGF) in inducing morphologic (cellular and subcellular) changes in the outer retina of carp was assessed. The effects of NGF on cone photomechanical movements (PMMs) and horizontal cell (HC) spinule formation were measured. NGF-induced cone contraction and formation of HC spinules in the dark-adapted retina were consistent with its role in light adaptation. These effects were dose dependent in the range of 5--250 nM. Because cone contraction and HC spinule formation have previously been shown to be controlled by dopamine (DA), nitric oxide (NO), or both, the possibility that the effects of NGF could be occurring by means of release of DA and/or NO was tested. Haloperidol (HAL), a nonspecific DA receptor blocker, or 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide potassium (cPTIO), a NO scavenger, was applied in combination with NGF to dark-adapted eyecups. The results showed that both HAL and cPTIO significantly blocked the effects of NGF on cone PMMs and HC spinule formation. In conclusion, (1) NGF represents a novel light-adaptive signalling mechanism in the outer retina of fish; and (2) NGF-induced cone contraction and HC spinule formation in the retina together with our previous observation would suggest that the effects of NGF may be mediated through NO by means of DA.

Adaptation, Ocular↗
PubMed2001

Voltage-gated K(+) channel activity in human prostate cancer cell lines of markedly different metastatic potential: distinguishing characteristics of PC-3 and LNCaP cells.

BACKGROUND: Although ion channels are known to contribute to a variety of basic cellular behaviors involved in the metastatic cascade, their role in metastasis per se has only recently been questioned. The hypothesis tested was whether K(+) channels were different between strongly metastatic PC-3 and weakly metastatic LNCaP human prostate cancer cell lines. METHODS: The whole-cell configuration of the patch clamp recording technique was used to record voltage-gated currents from LNCaP and PC-3 cell lines. The responses to different voltage-clamp protocols, sensitivity to external Ca(2+), and addition of drugs and toxins were explored. RESULTS: Voltage-gated K(+) current density was significantly larger in LNCaP than PC-3 cells. In addition, the K(+) currents in a sub-population of PC-3 cells were Ca(2+)-sensitive. These properties reflected the differential metastatic character of the cells, the PC-3 cells appearing potentially more "excitable". CONCLUSIONS: Prostate cancer cells of varying metastatic ability can be distinguished by their ion channel characteristics. The possible contribution(s) of K(+) channel activity to development of malignancy needs exploration.

Calcium Channels↗
PubMed2001

Use-dependent effects of amyloidogenic fragments of (beta)-amyloid precursor protein on synaptic plasticity in rat hippocampus in vivo.

The Alzheimer's disease-related beta-amyloid precursor protein (beta-APP) is metabolized to a number of potentially amyloidogenic peptides that are believed to be pathogenic. Application of relatively low concentrations of the soluble forms of these peptides has previously been shown to block high-frequency stimulation-induced long-term potentiation (LTP) of glutamatergic transmission in the hippocampus. The present experiments examined how these peptides affect low-frequency stimulation-induced long-term depression (LTD) and the reversal of LTP (depotentiation). We discovered that beta-amyloid peptide (Abeta1-42) and the Abeta-containing C -terminus of beta-APP (CT) facilitate the induction of LTD in the CA1 area of the intact rat hippocampus. The LTD was frequency- and NMDA receptor-dependent. Thus, although low-frequency stimulation alone was ineffective, after intracerebroventricular injection of Abeta1-42, it induced an LTD that was blocked by d-(-)-2-amino-5-phosphonopentanoic acid. Furthermore, an NMDA receptor-dependent depotentiation was induced in a time-dependent manner, being evoked by injection of CT 10 min, but not 1 hr, after LTP induction. These use- and time-dependent effects of the amyloidogenic peptides on synaptic plasticity promote long-lasting reductions in synaptic strength and oppose activity-dependent strengthening of transmission in the hippocampus. This will result in a profound disruption of information processing dependent on hippocampal synaptic plasticity.

Amyloid↗
PubMed2001

Isoforms of Na+, K+-ATPase in human prostate; specificity of expression and apical membrane polarization.

The cellular distribution of Na+, K+-ATPase subunit isoforms was mapped in the secretory epithelium of the human prostate gland by immunostaining with antibodies to the alpha and beta subunit isoforms of the enzyme. Immunolabeling of the alpha1, beta1 and beta2 isoforms was observed in the apical and lateral plasma membrane domains of prostatic epithelial cells in contrast to human kidney where the alpha1 and beta1 isoforms of Na+, K+-ATPase were localized in the basolateral membrane of both proximal and distal convoluted tubules. Using immunohistochemistry and PCR we found no evidence of Na+, K+-ATPase alpha2 and alpha3 isoform expression suggesting that prostatic Na+, K+-ATPase consists of alpha1/beta1 and alpha1/beta2 isozymes. Our immunohistochemical findings are consistent with previously proposed models placing prostatic Na+, K+-ATPase in the apical plasma membrane domain. Abundant expression of Na+, K+-ATPase in epithelial cells lining tubulo-alveoli in the human prostate gland confirms previous conclusions drawn from biochemical, pharmacological and physiological data and provides further evidence for the critical role of this enzyme in prostatic cell physiology and ion homeostasis. Na+, K+-ATPase most likely maintains an inwardly directed Na+ gradient essential for nutrient uptake and active citrate secretion by prostatic epithelial cells. Na+, K+-ATPase may also regulate lumenal Na+ and K+, major counter-ions for citrate.

Aged↗
PubMed2000

Toxic effect of the beta-amyloid precursor protein C-terminus fragment and Na+/Ca2+ gradients.

There is evidence to suggest that certain metabolic fragments of the beta-amyloid precursor protein (betaAPP) containing the whole of the beta-amyloid (Abeta) sequence are toxic to cells. We showed previously that the 105-amino acid C-terminal peptide (CT105) fragment, incorporating Abeta, is particularly toxic to Xenopus oocytes as well as to mammalian neurons. Here, we investigated the contributions of Na+ and Ca2+ gradients to intracellular CT105-induced toxicity in oocytes, monitored by measuring the membrane resting potential. The concentration gradients of Na+ and Ca2+ were manipulated to determine the involvement of the trans-membrane concentration gradients of these ions in the mode of action of CT105. The results suggested that Na+ influx and intracellular events are mainly responsible for the observed CT105-induced toxicity.

Amyloid beta-Protein Precursor↗
PubMed2000

Light-adaptive role of nitric oxide in the outer retina of lower vertebrates: a brief review.

The role of nitric oxide (NO) as a novel neurochemical mechanism controlling light adaptation of the outer retina is discussed by considering mainly published results. The emphasis is on the retinae of fishes and amphibia, but some data from the mammalian (rabbit) retinae have also been included for completeness. In the fish retina, application of NO donors in the dark caused light-adaptive photomechanical movements of cones. The normal effect of light adaptation in inducing cone contractions was suppressed by pretreatment of retinae with an NO scavenger. NO donors modulated horizontal cell activity by uncoupling the cells' lateral gap junctional interconnections and enhancing negative feedback to cones, again consistent with a light-adaptive role of NO. Direct evidence for light adaptation-induced release of NO has been obtained in fish (carp) and rabbit retinae. The results strongly suggest that control of retinal light adaptation is, under multiple neurochemical control, with NO and dopamine having an interactive role.

Adaptation, Physiological↗
PubMed2000

Effects of voltage-gated ion channel modulators on rat prostatic cancer cell proliferation: comparison of strongly and weakly metastatic cell lines.

BACKGROUND: The strongly metastatic MAT-LyLu and the weakly metastatic AT-2 rat prostatic cancer cell lines have been shown to express voltage-gated ion channels differentially. In the present study, the possible contribution of voltage-gated ion channel activity to the proliferation of these cell lines was investigated, in a comparative approach. METHODS: Several voltage-gated ion channel modulators were tested for their effects on proliferation over 54 hr, using an in vitro assay. The modes of action of the chemicals were monitored by electrophysiological (patch-clamp) recording. RESULTS: The voltage-gated K(+) channel blockers 4-aminopyridine (4-AP; 2 mM), margatoxin (5 nM), charybdotoxin (4.5 nM), and verapamil (50 microM) inhibited the K(+) channels of both cell lines by between 38-65% and reduced the proliferation of the AT-2 cell line, in a dose-dependent manner, by 8-51%. However, only 4-AP reduced proliferation of the MAT-LyLu cell line. Tetrodotoxin (6 microM) blocked completely the voltage-gated Na(+) channel expressed selectively in the MAT-LyLu cell line, but had no effect on the proliferation of either cell line. On the other hand, the presumed Na(+) channel "opener" veratridine (10-50 microM) reduced significantly, in a dose-dependent manner, the proliferation of both cell lines by up to approximately 30%. CONCLUSIONS: We conclude that the mechanism(s) controlling the proliferation of the weakly metastatic AT-2 cells involves voltage-gated K(+) channels. In contrast, the proliferation of strongly metastatic MAT-LyLu cells is much less dependent upon voltage-gated K(+) channel activity.

4-Aminopyridine↗
PubMed2000

Protein kinase and phosphatase modulation of quail brain GABA(A) and non-NMDA receptors co-expressed in Xenopus oocytes.

The GABA(A) receptor and the non-NMDA subtype of the ionotropic glutamate receptor were co-expressed in Xenopus oocytes by injection of quail brain mRNA. The oocytes were treated with various protein kinase (PK) and protein phosphatase (PP) activators and inhibitors and the effects on receptor functioning were monitored. Two phorbol esters, 4-beta-phorbol 12-myristate-13-acetate (PMA) and 4-beta-phorbol 12,13-dibutyrate (PDBu); the cGMP-dependent PK activators sodium nitroprusside (SNP) and S-nitrosoglutathione (SNOG); and the PP inhibitor okadaic acid (OA) reduced the amplitude of the GABA-induced currents, whilst the PK inhibitor staurosporine potentiated it. In addition, PMA, PDBu, SNP, and OA reduced the desensitization of the GABA-induced response. Identical treatments generally had similar but less pronounced effects on responses generated by kainate (KA) but the desensitization characteristic of the non-NMDA receptor was not affected. None of the treatments had any effect on the reversal potentials of the induced currents. Immunoblots revealed that the oocytes express endogenous PKG and guanylate cyclase. The results are discussed in terms of the molecular structures of GABA(A) and non-NMDA receptors and the potential functional consequences of phosphorylation/dephosphorylation.

Animals↗
PubMed2000

A study of membrane activity in rat prostate cancer cells: an evaluation of the FM1-43 dye technique.

A study was initiated to test whether the FM1-43 dye technique could be applied to the study of endocytic membrane activity in two rodent prostate cancer (MAT-LyLu and AT-2) cell lines of markedly different metastatic ability. The lipophilic dye FM1-43, which has frequently been used to monitor endo/exocytic activity in excitable cells was employed. We found, as in excitable tissues, that both strongly metastatic (MAT-LyLu) and weakly metastatic (AT-2) cells in culture take up FM1-43 to give vesicular staining of a variable pattern, which appeared to differ between the two cell lines. However, unlike excitable tissues, neither cell line subsequently released the dye. Indeed, both cell lines retained the dye through several rounds of cell division suggesting that dye incorporated by cells does not enter the endo/exocytotic cycle. Uptake of dye was independent of temperature, Na+/K+ gradients, pH or metabolism. We suggest that passive accumulation of FM1-43 can occur in cancer cells and should not, automatically, be interpreted as evidence of endocytosis.

Animals↗
PubMed2000

Electrophysiological recordings from the rat prostate gland in vitro: identified single-cell and transepithelial (lumen) potentials.

OBJECTIVE: To develop a preparation for the in vitro maintenance of the rat prostate gland and thus allow intracellular and transepithelial voltage measurements. MATERIALS AND METHODS: Ventral prostate glands from male rats were dissected free of connective tissue, separated into smaller lobes and maintained in vitro at 30 degrees C. Voltages were recorded with sharp micropipettes in identified cellular and luminal compartments, differentiated by several electrophysiological and histological parameters, including intracellular staining. RESULTS: Intracellular epithelial membrane potentials (median -40 mV) and transepithelial or luminal potentials (mean -4.2 mV) were recorded successfully. Luminal epithelial cells were dye-coupled. Prostate tissue could be maintained in vitro with no apparent electrophysiological or structural deterioration for up to approximately 7 h. CONCLUSION: Rat prostate tissue can be successfully maintained in vitro and electrophysiological recordings made from identified cellular compartments.

Action Potentials↗
PubMed1999

Effects of gadolinium ions upon rat prostatic cancer cell lines of markedly different metastatic potential.

The effects of gadolinium chloride, a non-specific blocker of mechanosensitive ion channels (MSICs), upon the motility and proliferation of two Dunning rat prostatic tumour cell lines of markedly different metastatic potential were investigated. Gadolinium (2-10 microM) caused a dose-dependent increase in the distance moved in 'wound' assays over a 48-h testing period. The highly metastatic MAT-LyLu cell line was significantly more sensitive to Gd3+, the weakly metastatic AT-2 cells responding only at the highest concentration (10 microM) used. There was no effect on the cells' proliferative rates. These data suggest that mechanosensitive channels could play a role in metastasis by modulating cell migration.

Animals↗
PubMed1999

Comparable effects of flickering and steady patterns of light adaptation on photomechanical responses of cones in amphibian (Xenopus laevis) retina.

The effects of two distinct patterns of light stimulus, steady and flicker, on cone photomechanical movements (PMMs) in the Xenopus laevis retina were investigated. For both patterns studied, the effects on PMMs were assessed by quantitative analysis of the cone positions in the outer retina. Steady light adaptation was found to be equally effective as flicker in causing cone contractions. This was unlike the situation previously found in the cyprinid fish retina, in which flickering light was significantly more effective than steady. This difference could be related to the light-evoked response characteristics and circuitry of dopaminergic retinal neurones in the two vertebrate classes. The role of dopamine and other possible neuromodulator(s) in light adaptive control of vertebrate retinae is discussed.

Adaptation, Ocular↗
PubMed1999

Tetrodotoxin suppresses morphological enhancement of the metastatic MAT-LyLu rat prostate cancer cell line.

Voltage-gated Na+ channels are expressed by highly metastatic MAT-LyLu cells, but not by poorly metastatic AT-2 cells, derived from the rodent Dunning model of prostatic cancer. We have investigated the possible involvement of these channels in the morphological development of the cells. Incubation of both the MAT-LyLu and the AT-2 cell line for 24 h with the Na+ channel blocker tetrodotoxin (TTX) at 6 microM altered the morphology only of the MAT-LyLu cell line. TTX produced significant decreases in: (a) cell process length and (b) field diameter, and increases in (c) cell body diameter and (d) process thickness. Importantly, 6 microM TTX had no significant effects on proliferation rates or cellular toxicity. The results suggest that Na+ channel activity plays a significant role in determining the morphological development of MAT-LyLu cells in such a way as to enhance their metastatic potential.

Animals↗
PubMed1998

Expression and localization in the fish retina of a homologue of the Alzheimer's related PS1 gene.

Early-onset familial Alzheimer's disease (early-onset FAD) has been linked with mutations in the presenilin gene, PS1. Mutations in PS1 may affect the processing/ trafficking of beta-amyloid precursor-protein (betaAPP) and favour the production of toxic amyloid-beta fragments that are associated with neural degeneration. This study reports the expression of a PS1-like cDNA in the carp (Cyprinus carpio) retina (the encoded protein shows 76% identity to the human PS1 protein). Carp PS1 mRNA was localized by in situ hybridization to the photoreceptor cell, inner nuclear and ganglion cell layers. Expression of the PS1 gene in the rat retina was also confirmed. The retinal expression of PS1 raises the possibility that PS1 mutations also lead to neural degeneration in the retina.

Amino Acid Sequence↗