Stress Regulates Aquaporin-8 Permeability to Impact Cell Growth and Survival

Abstract

Aquaporin-8 (AQP8) allows the bidirectional transport of water and hydrogen peroxide across biological membranes. Depending on its concentration, H 2 O 2 exerts opposite roles, amplifying growth factor signaling in physiological conditions, but causing severe cell damage when in excess. Thus, H 2 O 2 permeability is likely to be tightly controlled in living cells. Aims: In this study, we investigated whether and how the transport of H 2 O 2 through plasma membrane AQP8 is regulated, particularly during cell stress. Results: We show that diverse cellular stress conditions, including heat, hypoxia, and ER stress, reversibly inhibit the permeability of AQP8 to H 2 O 2 and water. Preventing the accumulation of intracellular reactive oxygen species (ROS) during stress counteracts AQP8 blockade. Once inhibition is established, AQP8-dependent transport can be rescued by reducing agents. Neither H 2 O 2 nor water transport is impaired in stressed cells expressing a mutant AQP8, in which cysteine 53 had been replaced by serine. Cells expressing this mutant are more resistant to stress-, drug-, and radiation-induced growth arrest and death. Innovation and Conclusion: The control of AQP8-mediated H 2 O 2 transport provides a novel mechanism to regulate cell signaling and survival during stress. Antioxid.

Candida utilis yeast as a functional protein source for Atlantic salmon (Salmo salar L.): Local intestinal tissue and plasma proteome responses

“…Our results confirm previous findings showing suppression of aqp8 gene expression in intestinal inflammatory processes in salmon such as SBMIE [13, 35]. The relation between aqp8 expression and inflammation is consistent with cell-based studies showing that reduced aqp8 expression is linked to increased oxidative cell stress damage [36] and implying that aqp8 is a key player in the maintenance of redox cellular status. DI.…”

Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: Oxidative eustress

“…The control of H 2 O 2 gradients by peroxiporins (see above) allows for further possibilities of fine-tuning with impact on cell signaling and survival, as shown for AQP8 [98]. AQP3 is required for Nox-derived H 2 O 2 signaling upon growth factor stimulation [99].…”

Clinically relevant radioresistant cells exhibit resistance to H2O2 by decreasing internal H2O2 and lipid peroxidation

“…AQP in plasma membranes function as water channels, 27 and it has been shown that AQP 1, 3, 8, and 9 permit the passage of H 2 O 2 . 23,[28][29][30] When the C53S mutation is observed in AQP8, the intake of H 2 O 2 decreases, and it has been reported that this mutation is involved in resistance to oxidative stress. 23 In this study, we looked for the presence of the AQP8 C53S mutation in CRR cells, but results were negative ( Figure S2).…”

“…AQP8 gene sequencing was performed to detect C53S mutation that had been shown to be resistant to H 2 O 2 treatment. 23 AQP8 gene sequencing showed no evidence of C53S mutation in either CRR or parental cells ( Figure S2(a)-(d)). Results also showed that AQP8 gene expression was downregulated in CRR cells.…”