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12 results on '"Linck, Valerie"'

4. Lovastatin attenuates hypertension induced by renal tubule‐specific knockout of ATP‐binding cassette transporter A1, by inhibiting epithelial sodium channels

Author

Wu, Ming‐Ming, primary, Liang, Chen, additional, Yu, Xiao‐Di, additional, Song, Bin‐Lin, additional, Yue, Qiang, additional, Zhai, Yu‐Jia, additional, Linck, Valerie, additional, Cai, Yong‐Xu, additional, Niu, Na, additional, Yang, Xu, additional, Zhang, Bao‐Long, additional, Wang, Qiu‐Shi, additional, Zou, Li, additional, Zhang, Shuai, additional, Thai, Tiffany L., additional, Ma, Jing, additional, Sutliff, Roy L., additional, Zhang, Zhi‐Ren, additional, and Ma, He‐Ping, additional

Published
2019
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5. Calcineurin A-α suppression drives nuclear factor-κB-mediated NADPH oxidase-2 upregulation.

Author

Cheriyan, Aswathy M., Ume, Adaku C., Francis, Cynthia E., King, Keyona N., Linck, Valerie A., Yun Bai, Hui Cai, Hoover, Robert S., Ma, Heping P., Gooch, Jennifer L., and Williams, Clintoria R.

Subjects
CAFFEIC acid, CALCINEURIN, NICOTINAMIDE adenine dinucleotide phosphate, TRANSCRIPTION factors, REACTIVE oxygen species, OXIDATIVE stress
Abstract

Calcineurin inhibitors (CNIs) are vital immunosuppressive therapies in the management of inflammatory conditions. A long-term consequence is nephrotoxicity. In the kidneys, the primary, catalytic calcineurin (CnA) isoforms are CnAα and CnAβ. Although the renal phenotype of CnAα-/- mice substantially mirrors CNI-induced nephrotoxicity, the mechanisms downstream of CnAα are poorly understood. Since NADPH oxidase-2 (Nox2)-derived oxidative damage has been implicated in CNI-induced nephrotoxicity, we hypothesized that CnAα inhibition drives Nox2 upregulation and promotes oxidative stress. To test the hypothesis, Nox2 regulation was investigated in kidneys from CnAα-/-, CnAβ-/-, and wild-type (WT) littermate mice. To identify the downstream mediator of CnAα, nuclear factor of activated T cells (NFAT) and NF-κ B regulation was examined. To test if Nox2 is transcriptionally regulated via a NF-κ B pathway, CnAa-/- and WT renal fibroblasts were treated with the NF-κ B inhibitor caffeic acid phenethyl ester. Our findings showed that cyclosporine A treatment induced Nox2 upregulation and oxidative stress. Furthermore, Nox2 upregulation and elevated ROS generation occurred only in CnAα-/- mice. In these mice, NF-κ B but not NFAT activity was increased. In CnAα-/- renal fibroblasts, NF-κ B inhibition prevented Nox2 upregulation and reactive oxygen species (ROS) generation. In conclusion, these findings indicate that 1) CnAα loss stimulates Nox2 upregulation, 2) NF-κ B is a novel CnAα-regulated transcription factor, and 3) NF-κ B mediates CnAα-induced Nox2 and ROS regulation. Our results demonstrate that CnAα plays a key role in Nox2 and ROS generation. Furthermore, these novel findings provide evidence of divergent CnA isoform signaling pathways. Finally, this study advocates for CnAα-sparing CNIs, ultimately circumventing the CNI nephrotoxicity. [ABSTRACT FROM AUTHOR]

Published
2021
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