The Radiobiological Characterization of Human and Porcine Lens Cells Suggests the Importance of the ATM Kinase in Radiation-Induced Cataractogenesis.
Joelle Al-ChoboqThibaud MathisJuliette Restier-VerletLaurène SonzogniLaura El NachefAdeline GranzottoMichel BourguignonNicolas ForayPublished in: Cells (2023)
Studies about radiation-induced human cataractogenesis are generally limited by (1) the poor number of epithelial lens cell lines available (likely because of the difficulties of cell sampling and amplification) and (2) the lack of reliable biomarkers of the radiation-induced aging process. We have developed a mechanistic model of the individual response to radiation based on the nucleoshuttling of the ATM protein (RIANS). Recently, in the frame of the RIANS model, we have shown that, to respond to permanent endo- and exogenous stress, the ATM protein progressively agglutinates around the nucleus attracted by overexpressed perinuclear ATM-substrate protein. As a result, perinuclear ATM crowns appear to be an interesting biomarker of aging. The radiobiological characterization of the two human epithelial lens cell lines available and the four porcine epithelial lens cell lines that we have established showed delayed RIANS. The BFSP2 protein, found specifically overexpressed around the lens cell nucleus and interacting with ATM, may be a specific ATM-substrate protein facilitating the formation of perinuclear ATM crowns in lens cells. The perinuclear ATM crowns were observed inasmuch as the number of culture passages is high. Interestingly, 2 Gy X-rays lead to the transient disappearance of the perinuclear ATM crowns. Altogether, our findings suggest a strong influence of the ATM protein in radiation-induced cataractogenesis.
Keyphrases
- radiation induced
- dna damage
- dna damage response
- dna repair
- radiation therapy
- endothelial cells
- protein protein
- amino acid
- stem cells
- small molecule
- mesenchymal stem cells
- induced pluripotent stem cells
- bone marrow
- cell death
- cell cycle arrest
- cell proliferation
- signaling pathway
- blood brain barrier
- tyrosine kinase
- label free
- heat stress