Data in support of sustained upregulation of adaptive redox homeostasis mechanisms caused by KRIT1 loss-of-function

Publication date: February 2018
Source:Data in Brief, Volume 16
Author(s): Cinzia Antognelli, Eliana Trapani, Simona Delle Monache, Andrea Perrelli, Claudia Fornelli, Francesca Retta, Paola Cassoni, Vincenzo Nicola Talesa, Saverio Francesco Retta
This article contains additional data related to the original research article entitled "KRIT1 loss-of-function induces a chronic Nrf2-mediated adaptive homeostasis that sensitizes cells to oxidative stress: implication for Cerebral Cavernous Malformation disease" (Antognelli et al., 2017) [1].Data were obtained by si-RNA-mediated gene silencing, qRT-PCR, immunoblotting, and immunohistochemistry studies, and enzymatic activity and apoptosis assays. Overall, they support, complement and extend original findings demonstrating that KRIT1 loss-of-function induces a redox-sensitive and JNK-dependent sustained upregulation of the master Nrf2 antioxidant defense pathway and its downstream target Glyoxalase 1 (Glo1), and a drop in intracellular levels of AP-modified Hsp70 and Hsp27 proteins, leading to a chronic adaptive redox homeostasis that sensitizes cells to oxidative DNA damage and apoptosis.In particular, immunoblotting analyses of Nrf2, Glo1, AP-modified Hsp70 and Hsp27 proteins, HO-1, phospho-c-Jun, phospho-ERK5, and KLF4 expression levels were performed both in KRIT1-knockout MEF cells and in KRIT1-silenced human brain microvascular endothelial cells (hBMEC) treated with the antioxidant Tiron, and compared with control cells. Moreover, immunohistochemistry analysis of Nrf2, Glo1, phospho-JNK, and KLF4 was performed on histological samples of human CCM lesions. Finally, the role of Glo1 in the downregulation of AP-modified Hsp70 and Hsp27 proteins, and the increase in apoptosis susceptibility associated with KRIT1 loss-of-function was addressed by si-RNA-mediated Glo1 gene silencing in KRIT1-knockout MEF cells.



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