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@PHDTHESIS{Richter:1022616,
author = {Richter, Anton},
othercontributors = {Gründer, Stefan and Huber, Michael},
title = {{U}ntersuchungen zum {ASIC}-abhängigen säureinduzierten
{Z}elltod},
school = {Rheinisch-Westfälische Technische Hochschule Aachen},
type = {Dissertation},
address = {Aachen},
publisher = {RWTH Aachen University},
reportid = {RWTH-2025-10125},
pages = {1 Online-Ressource : Illustrationen},
year = {2025},
note = {Veröffentlicht auf dem Publikationsserver der RWTH Aachen
University 2026; Dissertation, Rheinisch-Westfälische
Technische Hochschule Aachen, 2025},
abstract = {In 2015, the Wang et al. group postulated an acid-induced,
ASIC1a-dependent activation of the cell death mechanism
necroptosis. The aim of this study was to investigate
whether the ASIC1a:ASIC2a heteromer can also trigger
acid-induced necroptosis using LDH cytotoxicity assays and
whether this can be inhibited pharmacologically. Secondly,
the activation and phosphorylation of the necroptosis
cascade components RIPK1 and RIPK3 were to be examined for a
possible ASIC1a dependency using Western blotting. This also
involved possible temporal differences in phosphorylation
(0.5, 1, 3 and 6 h) as well as pharmacological
inhibitability. Different HeLa cell lines, such as HeLa wild
type and RIKP3-expressing HeLa cells, were used for the
experiments. Neither acid-induced necroptosis nor
pharmacological inhibition could be detected with the
heteromer ASIC1a:ASIC2a. In contrast to Wang et al., the
ASIC1a homomer also failed to demonstrate necroptosis and
protective inhibitory effects of Nec1s and PcTx1 at acidic
pH. In subsequent experiments, we modified the experimental
design, e.g. by extending the incubation time with acidic
medium or the proliferation time after transfection of
ASIC1a plasmids and by choosing a human ASIC1a plasmid in
addition to a rat plasmid. The observed effects, such as
apoptosis, were evaluated as probably non-specific. Western
blots showed no ASIC1a-dependent, acid-induced
phosphorylation of RIPK1 or RIPK3 within the 6-hour time
window. Thus, neither temporal differences nor inhibitory
effects of pharmacological substances such as Nec1s were
detected. In summary, no evidence of necroptosis by the
ASIC1a:ASIC2a heteromer or ASIC1a homomer and no
phosphorylation of RIP kinases 1 and 3 could be detected in
our setting. Many the observations were non-specific
effects. We were able to discuss possible reasons for this
in a multifaceted manner and discuss various suggestions for
protocol optimization to continue research towards the
promising acid-activated ASIC-dependent necroptosis.},
cin = {512000-2 ; 921410},
ddc = {610},
cid = {$I:(DE-82)512000-2_20140620$},
typ = {PUB:(DE-HGF)11},
doi = {10.18154/RWTH-2025-10125},
url = {https://publications.rwth-aachen.de/record/1022616},
}
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