The Protective Mechanism of TFAM on Mitochondrial DNA and its Role in Neurodegenerative Diseases

Song, Ying; Wang, Wenjun; Wang, Beibei; Shi, Qiwen

doi:10.1007/s12035-023-03841-7

Cited by 5 publications

(3 citation statements)

References 65 publications

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“…In our data, TFAM level was decreased by anticancer drugs. TFAM is an mtDNA-binding protein that is involved in repair; its levels decrease with DNA damage [ 57 , 58 , 59 , 60 ]. This suggests that mtDNA damage is induced by anticancer drugs targeting nucleic acids.…”

Section: Discussionmentioning

confidence: 99%

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Involvement of Ferroptosis Induction and Oxidative Phosphorylation Inhibition in the Anticancer-Drug-Induced Myocardial Injury: Ameliorative Role of Pterostilbene

Fujii,

Fujiwara-Tani,

Nukaga

et al. 2024

IJMS

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Patients with cancer die from cardiac dysfunction second only to the disease itself. Cardiotoxicity caused by anticancer drugs has been emphasized as a possible cause; however, the details remain unclear. To investigate this mechanism, we treated rat cardiomyoblast H9c2 cells with sunitinib, lapatinib, 5-fluorouracil, and cisplatin to examine their effects. All anticancer drugs increased ROS, lipid peroxide, and iron (II) levels in the mitochondria and decreased glutathione peroxidase-4 levels and the GSH/GSSG ratio. Against this background, mitochondrial iron (II) accumulates through the unregulated expression of haem oxygenase-1 and ferrochelatase. Anticancer-drug-induced cell death was suppressed by N-acetylcysteine, deferoxamine, and ferrostatin, indicating ferroptosis. Anticancer drug treatment impairs mitochondrial DNA and inhibits oxidative phosphorylation in H9c2 cells. Similar results were observed in the hearts of cancer-free rats treated with anticancer drugs in vitro. In contrast, treatment with pterostilbene inhibited the induction of ferroptosis and rescued the energy restriction induced by anticancer drugs both in vitro and in vivo. These findings suggest that induction of ferroptosis and inhibition of oxidative phosphorylation are mechanisms by which anticancer drugs cause myocardial damage. As pterostilbene ameliorates these mechanisms, it is expected to have significant clinical applications.

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Section: Discussionmentioning

confidence: 99%

“…This suggests that mtDNA damage is induced by anticancer drugs targeting nucleic acids. DOX, which has been well studied, and nucleic-acid-disrupting anticancer drugs cause damage to mtDNA [ 60 , 61 , 62 , 63 ]. Interestingly, SUN and LAP, which do not directly damage DNA, have been suggested to induce mtDNA damage.…”

Section: Discussionmentioning

confidence: 99%

Involvement of Ferroptosis Induction and Oxidative Phosphorylation Inhibition in the Anticancer-Drug-Induced Myocardial Injury: Ameliorative Role of Pterostilbene

Fujii,

Fujiwara-Tani,

Nukaga

et al. 2024

IJMS

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show abstract

“…Mitochondrial DNA must be maintained, expressed, and delivered. mtTFA also controls mitochondrial DNA transcription, stability, repair, and replication [ 69 ]. Oxygen radical stress oxidatively damages purine and pyrimidine bases and directly damages DNA, primarily through strand excision.…”

Section: Discussionmentioning

confidence: 99%

SGLT2 inhibitor as a potential therapeutic approach in hyperthyroidism-induced cardiopulmonary injury in rats

Bastawy,

El-Mosallamy,

Aljuaydi

et al. 2024

Pflugers Arch - Eur J Physiol

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Hyperthyroidism-induced cardiac disease is an evolving health, economic, and social problem affecting well-being. Sodium-glucose cotransporter protein 2 inhibitors (SGLT2-I) have been proven to be cardio-protective when administered in cases of heart failure. This study intended to investigate the potential therapeutic effect of SGLT2-I on hyperthyroidism-related cardiopulmonary injury, targeting the possible underlying mechanisms. The impact of the SGLT2-I, dapagliflozin (DAPA), (1 mg/kg/day, p.o) on LT4 (0.3 mg/kg/day, i.p)-induced cardiopulmonary injury was investigated in rats. The body weight, ECG, and serum hormones were evaluated. Also, redox balance, DNA fragmentation, inflammatory cytokines, and PCR quantification in heart and lung tissues were employed to investigate the effect of DAPA in experimentally induced hyperthyroid rats along with histological and immunohistochemical examination. Coadministration of DAPA with LT4 effectively restored all serum biomarkers to nearly average levels, improved ECG findings, and reinstated the redox balance. Also, DAPA could improve DNA fragmentation, elevate mtTFA, and lessen TNF-α and IGF-1 gene expression in both organs of treated animals. Furthermore, DAPA markedly improved the necro-inflammatory and fibrotic cardiopulmonary histological alterations and reduced the tissue immunohistochemical expression of TNF-α and caspase-3. Although further clinical and deep molecular studies are required before transposing to humans, our study emphasized DAPA’s potential to relieve hyperthyroidism-induced cardiopulmonary injury in rats through its antioxidant, anti-inflammatory, and anti-apoptotic effects, as well as via antagonizing the sympathetic over activity.

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Nimodipine ameliorates liver fibrosis via reshaping liver immune microenvironment in TAA-induced in mice

Guo,

Yang,

Zhao

et al. 2024

International Immunopharmacology

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The Protective Mechanism of TFAM on Mitochondrial DNA and its Role in Neurodegenerative Diseases

Cited by 5 publications

References 65 publications

Involvement of Ferroptosis Induction and Oxidative Phosphorylation Inhibition in the Anticancer-Drug-Induced Myocardial Injury: Ameliorative Role of Pterostilbene

Involvement of Ferroptosis Induction and Oxidative Phosphorylation Inhibition in the Anticancer-Drug-Induced Myocardial Injury: Ameliorative Role of Pterostilbene

SGLT2 inhibitor as a potential therapeutic approach in hyperthyroidism-induced cardiopulmonary injury in rats

Nimodipine ameliorates liver fibrosis via reshaping liver immune microenvironment in TAA-induced in mice

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