| 1. |
- EDSTRÖM, Anders, et al.
(author)
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Is protease activity involved in fast axonal transport?
- 1984
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In: Acta Physiologica Scandinavica. - : Wiley. - 0001-6772 .- 1365-201X. ; 121:4, s. 379-384
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Journal article (peer-reviewed)abstract
- N‐a‐p‐Tosyl‐L‐Lysine Chloromethyl Ketone (TLCK), a protease inhibitor, was found to irreversibly inhibit rapid axonal transport of protein in vitro in the frog sciatic nerve. TLCK exerted its action at the axonal level and seemed to depress the rate rather than the amount of transported protein. The efficiency of TLCK as a protease inhibitor was demonstrated by polyacrylamide gel electrophoresis, which showed that degradation of high molecular weight proteins (presumably neurofilament subunits) into a 25 000 dalton protein could be induced by exposing the frog nerves to triton‐X and prevented by the presence of TLCK. Findings that TLCK, at a transport inhibiting concentration (0.1 mM), had little or no effects on either protein synthesis or ATP levels, suggest that TLCK did not affect transport due to general cytotoxic properties. The effects of TLCK is discussed in relation to possible roles of protease activity in axonal transport.
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| 2. |
- EKSTRÖM, Per, et al.
(author)
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Effects of phenothiazines and dibenzazepines on axonal transport and microtubule assembly in vitro
- 1982
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In: Acta Physiologica Scandinavica. - : Wiley. - 0001-6772 .- 1365-201X. ; 116:2, s. 121-125
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Journal article (peer-reviewed)abstract
- Various phenothiazines (thioridazine, trifluoperazine and chlorpromazine) and dibenzazepines (lofepramine, amitriptyline and desipramine) were studied for effects on fast axonal transport (AXT) in vitro in frog sciatic nerves. AXT, measured as the accumulation of (3H) leucine‐labelled proteins in front of a ligature, was inhibited by more then 50% by all the drugs tested at 0.2 mM concentrations. Thioridazine and lofepramine were the most potent inhibitors. These effects were not due to decreased ganglionic incorporation. Some of the drugs also reduced the levels of high energy phosphates, adenosinetriphosphate (ATP) and creatinephosphate (CrP), but not to an extent which is likely to explain the arrested AXT. The polymerization of purified brain tubulin was inhibited by the phenothiazines but unaffected by the dibenzazepines at concentrations which inhibited AXT. Phenothiazines and dibenzazepines are chemically related and known to have a high affinity for calmodulin. The possibility that these drugs interefere with calmodulin regulated processes of importance for AXT will be discussed.
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| 3. |
- Ekström, Per, et al.
(author)
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Inhibition of Fast Axonal Transport by erythro‐9‐[3‐(2‐Hydroxynonyl)]Adenine
- 1984
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In: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 43:5, s. 1342-1345
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Journal article (peer-reviewed)abstract
- Abstract: erythro‐9‐[3‐(2‐Hydroxynonyl)]adenine, an inhibitor of protein carboxylmethylation and dynein‐ATPase activity, inhibited fast axonal transport in vitro in frog sciatic nerves. Its site of action might be associated with an ATPase on which transport depends, since specific carboxylmethylation inhibitors lacked effects on transport. The levels of high energy phosphates and protein synthesis were unaffected by the drug at a transport‐inhibiting concentration, making disturbances due to metabolic effects less likely. An erythro‐9‐[3‐(2‐hy‐droxynonyl)]adenine‐sensitive ATPase was looked for in various nerve fractions but has so far not been resolved.
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| 4. |
- Kanje, Martin, et al.
(author)
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Divalent cations and fast axonal transport in chemically desheathed (triton X-treated) frog sciatic nerve
- 1982
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In: Brain Research. - 0006-8993. ; 241:1, s. 67-74
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Journal article (peer-reviewed)abstract
- We have studied the ability of divalent cations to restore to normal axonal transport (AXT) which was inhibited by deprivation of Ca2+ and/or Mg2+ ions. The epi- and perineurium of the frog sciatic nerve were damaged by a 30-s wash in Triton X-100 containing frog Ringer's. This treatment did not affect either AXT or nerve levels of Ca2+ and Mg2+, but made the ions more easily extractable with a Ca2+- and Mg2+-free Ringer's solution (CMFR). Inhibition of AXT was achieved by incubating Triton X-100-treated nerves in CMFR + EGTA for 5 h, followed by an additional incubation for 12 h in CMFR or Ringer's devoid of only Ca2+ (CFR). These treatments reduced Ca2+ and Mg2+ contents by 77% and 38% respectively. Addition of Ca2+ (1.1 mM) during the 12-h period stimulated AXT, measured as accumulation of 3H-labelled components in front of a ligature, several fold. Mg2+ could not substitute for Ca2+ but potentiated the stimulating effect of Ca2+. Addition of other divalent cations did not affect AXT (Sr2+ and Ba2+) or potentiated the inhibition caused by Ca2+-deprived medium (Mn2+ and Co2+). ATP and creatine phosphate contents were similar in nerves incubated in Ca2+-deprived medium and in Ca2+-containing Ringer's. Thus, inhibition of AXT in the former situation was not due to a decreased availability of high energy phosphates. Two calcium antagonists, D-600 and nifedipin, which are potent smooth muscle relaxants, effectively blocked AXT. The present ressults suggest that Ca2+ is specifically required to maintain AXT and that an anlogy exists between Ca2+ regulation during smooth muscle contraction and AXT.
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| 5. |
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| 6. |
- Kjellstrand, P., et al.
(author)
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Perchloroethylene: Effects on body and organ weights and plasma buturylcholinesterase activity in mice
- 1984
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In: Acta Pharmacologica et Toxicologica. - : Wiley. - 0001-6683. ; 54:5, s. 414-424
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Journal article (peer-reviewed)abstract
- The effects of continuous and intermittent inhalation of perchloroethylene (PCE) on plasma butyrylcholinesterase (BuChE) activity, organ weights, liver morphology and motor activity in mice (strain NMRI) were tested. PCE exposure increased plasma BuChE activity in a time- and concentration dependent manner in both sexes. The increase was statistically significant at 37 p.p.m. in animals continuously exposed for 30 days. BuChE increased approximately 1.5 times in females and 2.5 times in males after 120 days exposure to 150 p.p.m. After rehabilitation of animals exposed for 30 days to 150 p.p.m., BuChE levels returned to normal. Liver weight also increased in a time and concentration dependent manner. Both sexes exhibited significant liver enlargement at 9 p.p.m. The increase was about 2.3 in females and 1.9 in males after continuous exposure to 150 p.p.m. for 120 days. After rehabilitation (120 days) of animals exposed to 150 p.p.m. for 30 days, a 10% increase still remained. A decrease in body weight gain was seen in both sexes after exposure to concentrations above 75 p.p.m. Female kidney weight was slightly increased. No clear effect on spleen weight could be detected. When the same time-weighted average concentration was used, intermittent exposure for 30 days had similar effects on liver weight and BuChE activity as continuous exposure, even when exposures lasted for only one hour per day. Liver cell morphology was changed after PCE exposure. The alterations could be observed already at 9 p.p.m. but disappeared after rehabilitation.
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| 7. |
- Kjellstrand, Per, et al.
(author)
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Trichloroethylene: Effects on body and organ weights in mice, rats and gerbils
- 1981
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In: Toxicology. - 0300-483X. ; 21:2, s. 105-115
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Journal article (peer-reviewed)abstract
- The influence of continuous inhalation of 150 ppm trichloroethylene (TCE) on body, liver, spleen, and kidney weights in rats, mice, and mongolian gerbils was tested. An age dependent decrease in body weight gain was observed in female rats exposed to TCE. All 3 spcies showed liver enlargement caused by the exposure. The effect was much more pronounced in mice, in which the increase was 60–80%, than in rats and gerbils where it was only 20–30%. After the end of the TCE-exposure the liver weights of the mice decreased rapidly. After 5 days of rehabilitation to the weight was only 10–20% higher than that of the controls. This difference persisted for at least 25 days. The spleen weight appeared unaffected or somewhat smaller in TCE-exposed animals of all species. An increased kidney weight (15%) was observed in TCE-exposed gerbils. This effect was less pronounced in mice and rats. Effects on the liver have earlier been seen only after exposure to concentrations much higher than that used in the present study. This difference is results in proposed to be due to the different schedules used for the exposure.
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| 8. |
- Kjellstrand, Per, et al.
(author)
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Trichloroethylene: Further studies of the effect on body and organ weights and plasma buturylcholinesterase activity in mice
- 1983
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In: Acta Pharmacologica et Toxicologica. - : Wiley. - 0001-6683. ; 53:5, s. 375-384
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Journal article (peer-reviewed)abstract
- The effects of continuous and intermittent inhalation of trichloroethylene (TCE) were studied in male and female mice. Plasma butyrylcholinesterase (BuChE) activity, body, liver, kidney and spleen weights were measured. The liver was studied histologically and motor activity measured with doppler radar. Continuous TCE-exposure (37–300 p.p.m.) increased plasma BuChE activity in the males in a time and concentration dependent manner. After 30 days at 37 p.p.m. the increase was about 25%. Exposure to 300 p.p.m. for 30 days increased the activity three times. BuChE activity in females was only slightly influenced even at 300 p.p.m. Liver weight was increased in a time and concentration dependent manner in both sexes. In animals continuously exposed for 30 days to 300 p.p.m., liver weight was roughly twice that of the air-exposed controls. Morphological changes were observed in the liver of TCE-exposed animals. Above 150 p.p.m. kidney weight in both sexes was significantly increased. This effect was more pronounced in the males than in the females. Spleen weight was not influenced by the exposure. Body weight increase was slightly lower in exposed animals. Plasma BuChE activity and liver weight returned to normal when exposure was terminated. Intermittent exposure to short pulses of high concentration of TCE had roughly the same effect on BuChE, body and organ weights as continuous exposure to the same time-weighted average. Motor activity was affected by the intermittent exposure schedules. At 900 p.p.m. decrease in activity was observed. At 3600 p.p.m. motor activity was considerably increased.
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