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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},
}