Downregulation of catalase by reactive oxygen species via PI 3 kinase/Akt signaling in mesangial cells

Abstract

Reactive oxygen species (ROS) contribute to many glomerular diseases by targeting mesangial cells. ROS have been shown to regulate expression of many antioxidant enzymes including catalase. The mechanism by which the expression of catalase protein is regulated by ROS is not precisely known. Here we report that increased intracellular ROS level by hydrogen peroxide (H(2)O(2)) reduced the expression of catalase. H(2)O(2) increased phosphorylation of Akt kinase in a dose-dependent and sustained manner with a concomitant increase in the phosphorylation of FoxO1 transcription factor. Further analysis revealed that H(2)O(2) promoted rapid activation of phosphatidylinositol (PI) 3 kinase. The PI 3 kinase inhibitor Ly294002 and expression of tumor suppressor protein PTEN inhibited Akt kinase activity, resulting in the attenuation of FoxO1 phosphorylation and preventing the downregulating effect of H(2)O(2) on catalase protein level. Dominant negative Akt attenuated the inhibitory effect of H(2)O(2) on expression of catalase. Constitutively active FoxO1 increased the expression of catalase. However, dominant negative FoxO1 inhibited catalase protein level. Catalase transcription was reduced by H(2)O(2) treatment. Furthermore, expression of dominant negative Akt and constitutively active FoxO1 increased catalase transcription, respectively. These results demonstrate that ROS downregulate the expression of catalase in mesangial cells by PI 3 kinase/Akt signaling via FoxO1 as a target.

Tumour suppressor PTEN enhanced enzyme activity of GPx, SOD and catalase by suppression of PI3K/AKT pathway in non-small cell lung cancer cell lines

“…Obtained data implicates that PTEN up-regulates antioxidant enzyme activity via inhibition of PI3K/ AKT pathway by its lipid dephosphatase activity in PC14 cells. These results are in good agreement with previous reports 25,26 . Venkatesan et al 25 reported that PI3K/AKT pathway activation down-regulate catalase activity and Choi et al 21 also showed that gemsitabin inhibition of NFκB activity leads to an increase in SOD and catalase activity.…”

“…These results are in good agreement with previous reports 25,26 . Venkatesan et al 25 reported that PI3K/AKT pathway activation down-regulate catalase activity and Choi et al 21 also showed that gemsitabin inhibition of NFκB activity leads to an increase in SOD and catalase activity. Moreover, Leung et al 26 reported that antioxidant enzyme activity was involved in apoptosis in human lung squamous carcinoma CH27 cells.…”

“…Previously published data show that catalase enzyme activity can down-regulate PI3K/AKT signaling in mesangial cells. Venkatesan et al 25 and Choi et al 21 showed that when NFκB activity was suppressed with gemsitabin, SOD and catalase activity increase in macrophages. With reference to these data, we hypothesized that PTEN could possibly regulate antioxidant enzyme activity by inhibition of PI3K/AKT/NFκB pathway.…”

Intracellular reactive oxygen species are essential for PI3K/Akt/mTOR-dependent IL-7-mediated viability of T-cell acute lymphoblastic leukemia cells

“…This does not exclude the possibility that IL-7 can increase ROS levels in T-ALL cells via Akt-mediated phosphorylation and inhibition of FOXO transcription factors, which are critical negative regulators of oxidative stress. [42][43][44] Taking together our current and previously published data, 5 we propose a model (Supplementary Figure S6), whereby IL-7 rapidly induces minor upregulation and/or recruitment of ROS that is required for early PI3K/Akt/mTOR signaling pathway activation in an NADPH oxidase-independent, mitochondrial respiration-reliant manner. In turn, PI3K/Akt/mTOR-mediated signaling leads to Glut1 upregulation and glucose uptake that are mandatory for late IL-7-mediated ROS upregulation.…”

Involvement of c-Met- and Phosphatidylinositol 3-Kinase Dependent Pathways in Arsenite-Induced Downregulation of Catalase in Hepatoma Cells

“…Venkatesan et al examined the role of PI3K/Akt in H 2 O 2 -induced downregulation of catalase in mesangial cells. 20) They found that LY significantly attenuates the inhibitory effect of H 2 O 2 on the level of catalase protein and that the expression of the tumor suppressor protein phosphatase and tensin homolog (PTEN), a modulator of PI3K pathway, 21,22) increases catalase protein levels. It is the expression of dominant negative Akt that significantly activates the catalase gene promoter and prevents the inhibitory effect of H 2 O 2 on the catalase protein level.…”