@article{MTMT:1250912,
title = {The role of calpain-mediated spectrin proteolysis in traumatically induced axonal injury.},
url = {https://m2.mtmt.hu/api/publication/1250912},
author = {Büki, András and Siman, R and Trojanowski, JQ and Povlishock, JT},
doi = {10.1097/00005072-199904000-00007},
journal-iso = {J NEUROPATH EXP NEUR},
journal = {JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY},
volume = {58},
unique-id = {1250912},
issn = {0022-3069},
abstract = {In animals and man, traumatic brain injury (TBI) results in axonal injury (AI)
that contributes to morbidity and mortality. Such injured axons show progressive
change leading to axonal disconnection. Although several theories implicate
calcium in the pathogenesis of AI, experimental studies have failed to confirm
its pivotal role. To explore the contribution of Ca2+-induced proteolysis to
axonal injury, this study was undertaken in an animal model of TBI employing
antibodies targeting both calpain-mediated spectrin proteolysis (CMSP) and focal
neurofilament compaction (NFC), a marker of intra-axonal cytoskeletal
perturbation, at 15-120 minutes (min) postinjury. Light microscopy (LM) revealed
that TBI consistently evoked focal, intra-axonal CMSP that was spatially and
temporally correlated with NFC. These changes were seen at 15 min postinjury with
significantly increasing number of axons demonstrating CMSP immunoreactivity over
time postinjury. Electron microscopy (EM) demonstrated that at 15 min postinjury
CMSP was confined primarily to the subaxolemmal network. With increasing survival
(30-120 min) CMSP filled the axoplasm proper. These findings provide the first
direct evidence for focal CMSP in the pathogenesis of generalized/diffuse AI.
Importantly, they also reveal an initial subaxolemmal involvement prior to
induction of a more widespread axoplasmic change indicating a spatial-temporal
compartmentalization of the calcium-induced proteolytic process that may be
amenable to rapid therapeutic intervention.},
year = {1999},
eissn = {1554-6578},
pages = {365-375}
}
@article{MTMT:1250932,
title = {Cyclosporin a limits calcium-induced axonal damage following traumatic brain injury.},
url = {https://m2.mtmt.hu/api/publication/1250932},
author = {Okonkwo, DO and Büki, András and Siman, R and Povlishock, JT},
doi = {10.1097/00001756-199902050-00026},
journal-iso = {NEUROREPORT},
journal = {NEUROREPORT},
volume = {10},
unique-id = {1250932},
issn = {0959-4965},
abstract = {In traumatic axonal injury, Ca2+ influx across a focally damaged axolemma
precipitates local mitochondrial failure, degradation of the subaxolemmal
spectrin network and compaction of neurofilaments, which collectively contribute
to axonal failure. In previous studies, cyclosporin A pretreatment preserved
mitochondrial integrity and attenuated axonal failure following trauma. Here we
investigate whether this CsA-linked protection was related to the concomitant
blunting of intra-axonal, Ca2+-induced cytoskeletal changes in traumatic axonal
injury, assessed with antibodies targeting spectrin proteolysis and neurofilament
compaction. CsA pretreatment dramatically reduced Ca2+-induced cytoskeletal
damage following injury; CsA-treated rats, compared with vehicle-treated rats,
displayed a 70% decrease in immunoreactive/damaged profiles. We suggest that
CsA-mediated preservation of mitochondrial integrity enables the restoration of
ionic and metabolic homeostasis thereby short-circuiting Ca2+-induced proteolysis
in injured axons.},
year = {1999},
eissn = {1473-558X},
pages = {353-358}
}
@article{MTMT:1446457,
title = {Modulation of Ca2+ influx dependent on store depletion by intracellular adenine-guanine nucleotide levels},
url = {https://m2.mtmt.hu/api/publication/1446457},
author = {Gamberucci, A and Innocenti, B and Fulceri, R and Bánhegyi, Gábor and Giunti, R and Pozzan, T and Benedetti, A},
journal-iso = {J BIOL CHEM},
journal = {JOURNAL OF BIOLOGICAL CHEMISTRY},
volume = {269},
unique-id = {1446457},
issn = {0021-9258},
abstract = {The effects of a number of metabolic inhibitors on the influx of Ca2+ activated by stimulation of receptors coupled to inositol 1,4,5- trisphosphate generation or by depletion of intracellular Ca2+ stores with thapsigargin were investigated in four different cell types: Ehrlich ascites tumor cells, Jurkat and HeLa cell lines, and rat hepatocytes. Independently of their chemical structure and site of inhibition, all of these metabolic poisons markedly inhibited Ca2+ influx without significantly affecting Ca2+ release. This inhibition was not due to membrane potential depolarization or to alteration in cytosolic pH but appeared correlated to a drop in the cellular concentration of ATP. The decreases in cellular [ATP] were paralleled by decreases in [GTP] and by increases in [ADP] and [GDP]. The reduction in ATP level necessary to drastically reduce Ca2+ influx was quite small, e.g. a 50% inhibition for a 5% reduction in [ATP], thus within the range of fluctuation presumably occurring under physiological conditions. We suggest that changes in the adenine or guanine nucleotide concentrations may represent an important modulatory mechanism of Ca2+ influx activated by store depletion.},
keywords = {Male; HISTAMINE; metabolism; calcium; MICE; INOSITOL 1,4,5-TRISPHOSPHATE; RATS; ARTICLE; MOUSE; ADENINE; human; animal; Rats, Sprague-Dawley; priority journal; GLUCOSE; Support, Non-U.S. Gov't; regulatory mechanism; PHYTOHEMAGGLUTININ; Calcium ion; Vasopressins; rat strain; Manganese; Guanine; Cell Line; human cell; oligomycin; Adenosine Triphosphate; calcium cell level; bradykinin; thapsigargin; Phytohemagglutinins; terpene; leukemia cell line; transport kinetics; adenine nucleotides; calcium transport; cell pH; Terpenes; Oligomycins; Guanine Nucleotides; Ca(2+)-Transporting ATPase; hela cell; cell membrane depolarization; calcium mobilization; vasopressin derivative; rotenone; guanine nucleotide; Ca(2+) Transporting ATPase; adenosine triphosphatase (calcium); adenine nucleotide; inositol 1,4,5 trisphosphate; guanosine triphosphate; rat},
year = {1994},
eissn = {1083-351X},
pages = {23597-23602},
orcid-numbers = {Bánhegyi, Gábor/0000-0001-7559-0066}
}