Iron Overload Induces Oxidative Stress, Cell Cycle Arrest and Apoptosis in Chondrocytes

Acute myelogenous leukemia (AML) is a disease that severely affects the physical health of children. Thus, we aimed to identify biomarkers associated with AML prognosis in children. Using transcriptomics on an mRNA dataset from 27 children with non-M3 AML, we selected genes from among those with the top 5000 median absolute deviation (MAD) values for subsequent analysis which showed that two modules were associated with AML risk groups. Thus, enrichment analysis was performed using genes from these modules. A one-way Cox analysis was performed on a dataset of 149 non-M3 AML patients downloaded from the TCGA. This identified four genes as significant: FTH1, RCC2, ABHD17B, and IRAK1. Through survival analysis, FTH1 was identified as a key gene associated with AML prognosis. We verified the proliferative and regulatory effects of ferroptosis on MOLM-13 and THP-1 cells using Liproxstatin-1 and Erastin respectively by CCK-8 and flow cytometry assays. Furthermore, we assayed expression levels of FTH1 in MOLM-13 and THP-1 cells after induction and inhibition of ferroptosis by real-time quantitative PCR, which showed that upregulated FTH1 expression promoted proliferation and inhibited apoptosis in leukemia cells. In conclusion, high expression of FTH1 promoted proliferation and inhibited apoptosis of leukemic cells through the ferroptosis pathway and is thus a potential risk factor that affects the prognosis of non-M3 AML in children.

show abstract

“…FTH1 plays an anti-cancer role by promoting angiogenesis ( 39 , 40 ). Increased expression of FTH1 inhibits cancer by promoting apoptosis ( 41 ).…”

Section: Discussionmentioning

confidence: 99%

High expression level of the FTH1 gene is associated with poor prognosis in children with non-M3 acute myeloid leukemia

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Transforming growth factor β 1 can protect chondrocytes from oxidative stress by regulating autophagy (Kurakazu et al, 2021). Karim et al found that iron overload in chondrocytes can induce oxidative stress, cell cycle arrest and apoptosis (Karim et al, 2022). Pang et al found that Bardoxolonemethyl can inhibit chondrocyte apoptosis and ECM degradation induced by oxidative stress in vitro, and reduce OA in vivo (Pang et al, 2021).…”

Section: How To Solve the Oxidative Stress In Knee Osteoarthritismentioning

confidence: 99%

The role of oxidative stress in the development of knee osteoarthritis: A comprehensive research review

Liu

Luo²,

Yang³

et al. 2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

Knee osteoarthritis (KOA) is one of the most common degenerative diseases, and its core feature is the degeneration and damage of articular cartilage. The cartilage degeneration of KOA is due to the destruction of dynamic balance caused by the activation of chondrocytes by various factors, with oxidative stress playing an important role in the pathogenesis of KOA. The overproduction of reactive oxygen species (ROS) is a result of oxidative stress, which is caused by a redox process that goes awry in the inherent antioxidant defence system of the human body. Superoxide dismutase (SOD) inside and outside chondrocytes plays a key role in regulating ROS in cartilage. Additionally, synovitis is a key factor in the development of KOA. In an inflammatory environment, hypoxia in synovial cells leads to mitochondrial damage, which leads to an increase in ROS levels, which further aggravates synovitis. In addition, oxidative stress significantly accelerates the telomere shortening and ageing of chondrocytes, while ageing promotes the development of KOA, damages the regulation of redox of mitochondria in cartilage, and stimulates ROS production to further aggravate KOA. At present, there are many drugs to regulate the level of ROS, but these drugs still need to be developed and verified in animal models of KOA. We discuss mainly how oxidative stress plays a part in the development of KOA. Although the current research has achieved some results, more research is needed.

show abstract

“…Iron overload is typically detected by measuring serum transferrin saturation (the amount of ferric iron bound to the carrier protein transferrin in the circulation; >45 percent indicates iron excess) in conjunction with serum ferritin concentration ( 35 ). Iron overload has been shown to hasten bone loss in healthy postmenopausal women and middle-aged men, increase apoptosis, and impair chondrocyte functional competence ( 38 , 39 ). Furthermore, aberrant iron accumulation causes nerve injury in rats by up-regulating CXCL10/CXCR3 signaling in the spinal dorsal horn, resulting in mechanical allodynia and thermal hyperalgesia ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

Causal associations of iron status and back pain risk: A Mendelian randomization study

Tang

et al. 2022

Front. Nutr.

View full text Add to dashboard Cite

BackgroundObservational studies have previously suggested a link between iron status makers and back pain. We conducted a two-sample Mendelian randomization (MR) study to determine the putative causal relationship between systemic iron status and back pain.Materials and methodsIn this MR study, a genome-wide association study (GWAS) involving 48,972 individuals was used to identify genetic instruments highly associated with systemic iron status. The outcome data (back pain) were derived from the Neale Lab consortium’s summary data from the UK Biobank (85,221 cases and 336,650 controls). With the inverse variance weighted (IVW) method as the main analysis, conservative analyses (selecting SNPs with concordant change of iron status biomarkers) and liberal analyses (selecting SNPs with genome-wide significant association with each iron status biomarker) were carried out. For sensitivity analyses, the MR-Egger, MR-Egger intercept, weighted median, weighted mode, and MR based on a Bayesian model averaging approaches were used. The Cochran’s Q-test was used to detect heterogeneity.ResultsBack pain was associated with genetically instrumented serum iron (OR = 1.01; 95% CI = 1.00–1.02, p = 0.01), ferritin (OR = 1.02; 95% CI = 1.00–1.04, p = 0.02), and transferrin saturation (OR = 1.01; 95% CI = 1.00–1.01, p = 0.01). Furthermore, there was no evidence of a link between transferrin and the risk of back pain (OR = 0.99, 95% CI = 0.98–1.00, p = 0.08). The sensitivity analyses and Cochran’s Q-test indicated that no pleiotropy or heterogeneity was detected (all p > 0.05).ConclusionWe provided potential genetic evidences for the causal associations of iron status with increased incidence of back pain. However, the evidences were weakened due to the low power. Further larger MR studies or RCTs are needed to investigate small effects.

show abstract

Iron Overload Induces Oxidative Stress, Cell Cycle Arrest and Apoptosis in Chondrocytes

Cited by 22 publications

References 43 publications

High expression level of the FTH1 gene is associated with poor prognosis in children with non-M3 acute myeloid leukemia

High expression level of the FTH1 gene is associated with poor prognosis in children with non-M3 acute myeloid leukemia

The role of oxidative stress in the development of knee osteoarthritis: A comprehensive research review

Causal associations of iron status and back pain risk: A Mendelian randomization study

Contact Info

Product

Resources

About