ArticleCellular & molecular biology letters2013
Pharmacological inhibition of GSK3 attenuates DNA damage-induced apoptosis via reduction of p53 mitochondrial translocation and Bax oligomerization in neuroblastoma SH-SY5Y cells.
Article in Cellular & molecular biology letters, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 52 citations in OpenAlex.
- Loss of genome maintenance is linked to mTOR complex 1 signaling and accelerates podocyte damage.JCI insight · 2025Article
- Cisplatin-Induced APE2 Overexpression Disrupts MYH9 Function and Causes Hearing Loss.Cancer research communications · 2025Article
- Recent Developments in Metal-Based Drugs and Chelating Agents for Neurodegenerative Diseases Treatments.International journal of molecular sciences · 2019Review
- Cilostazol Mediated Nurr1 and Autophagy Enhancement: Neuroprotective Activity in Rat Rotenone PD Model.Molecular neurobiology · 2018Article
- In vivo and ex vivo analyses of amyloid toxicity in the Tc1 mouse model of Down syndrome.Journal of psychopharmacology (Oxford, England) · 2018Article
- Article
- An Oldie but Goodie: Lithium in the Treatment of Bipolar Disorder through Neuroprotective and Neurotrophic Mechanisms.International journal of molecular sciences · 2017Review
- Neuroprotective Functions for the Histone Deacetylase SIRT6.Cell reports · 2017Article
- Therapeutic Mechanisms of Lithium in Bipolar Disorder: Recent Advances and Current Understanding.CNS drugs · 2016Review
- A new look at an old drug: neuroprotective effects and therapeutic potentials of lithium salts.Neuropsychiatric disease and treatment · 2016Review
- RNA silencing of integrin-linked kinase increases the sensitivity of the A549 lung cancer cell line to cisplatin and promotes its apoptosis.Molecular medicine reports · 2015Article
- Heat stress induced apoptosis is triggered by transcription-independent p53, Ca(2+) dyshomeostasis and the subsequent Bax mitochondrial translocation.Scientific reports · 2015Article
- Lithium enhanced cell proliferation and differentiation of mesenchymal stem cells to neural cells in rat spinal cord.International journal of clinical and experimental pathology · 2015Article
- Neuroprotective effects of lithium: implications for the treatment of Alzheimer's disease and related neurodegenerative disorders.ACS chemical neuroscience · 2014Review
- Association of glycogen synthase kinase-3β with Parkinson's disease (review).Molecular medicine reports · 2014Review
- Specific glycogen synthase kinase-3 inhibition reduces neuroendocrine markers and suppresses neuroblastoma cell growth.Cancer biology & therapy · 2014Article
- Wnt and lithium: a common destiny in the therapy of nervous system pathologies?Cellular and molecular life sciences : CMLS · 2014Review
- Decay of γ-H2AX foci correlates with potentially lethal damage repair and P53 status in human colorectal carcinoma cells.Cellular & molecular biology letters · 2014Article
- Sodium glucose cotransporter 1 ligand BLF501 as a novel tool for management of gastrointestinal mucositis.Molecular cancer · 2014Article
- GSK-3 and mitochondria in cancer cells.Frontiers in oncology · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glycogen synthase kinase-3 (GSK3) and p53 play crucial roles in the mitochondrial apoptotic pathway and are known to interact in the nucleus. However, it is not known if GSK3 has a regulatory role in the mitochondrial translocation of p53 that participates in apoptotic signaling following DNA damage. In this study, we demonstrated that lithium and SB216763, which are pharmacological inhibitors of GSK3, attenuated p53 accumulation and caspase-3 activation, as shown by PARP cleavage induced by the DNA-damaging agents doxorubicin, etoposide and camptothecin. Furthermore, each of these agents induced translocation of p53 to the mitochondria and activated the mitochondrial pathway of apoptosis, as evidenced by the release of cytochrome C from the mitochondria. Both mitochondrial translocation of p53 and mitochondrial release of cytochrome C were attenuated by inhibition of GSK3, indicating that GSK3 promotes the DNA damage-induced mitochondrial translocation of p53 and the mitochondrial apoptosis pathway. Interestingly, the regulation of p53 mitochondrial translocation by GSK3 was only evident with wild-type p53, not with mutated p53. GSK3 inhibition also reduced the phosphorylation of wild-type p53 at serine 33, which is induced by doxorubicin, etoposide and camptothecin in the mitochondria. Moreover, inhibition of GSK3 reduced etoposide-induced association of p53 with Bcl2 and Bax oligomerization. These findings show that GSK3 promotes the mitochondrial translocation of p53, enabling its interaction with Bcl2 to allow Bax oligomerization and the subsequent release of cytochrome C. This leads to caspase activation in the mitochondrial pathway of intrinsic apoptotic signaling.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.