Protection of chlorophyllin against oxidative damage by inducing HO-1 and NQO1 expression mediated by PI3K/Akt and Nrf2

Abstract

Green vegetables are thought to have a chemoprotective effect on the basis of epidemiologic evidence. This study investigated whether chlorophyllin (CHL) could induce antioxidant enzymes and confer protection against oxidative damage. The results showed that CHL could induce HO-1 and NQO1 expression in human umbilical vein endothelial cell (HUVEC) in a time- and dose-dependent manner and protect them against hydrogen peroxide caused oxidative damage. The induction of HO-1 and NQO1 by CHL was accompanied with the accumulation of transcription factor Nrf2 in nucleus and the activation of PI3K/Akt signalling pathway. Additionally, the specific inhibitor of PI3K/Akt could obviously decrease not only the induced expression of HO-1 and NQO1 but also the antioxidant effect of CHL. In conclusion, this study proved that CHL exerts antioxidant effect by inducing HO-1 and NQO1 expression mediated by PI3K/Akt and Nrf2. One thinks CHL may have promise to be prophylactic pharmaceuticals without adverse effects.

High Glucose Promotes Tumor Invasion and Increases Metastasis-Associated Protein Expression in Human Lung Epithelial Cells by Upregulating Heme Oxygenase-1 via Reactive Oxygen Species or the TGF-β1/PI3K/Akt Signaling Pathway

“…This finding is supported by previous reports that HG induced TGF-β generation [11] and that TGF-β1 up-regulated HO-1 expression via the PI3K/Akt signaling pathway [43]. However, our results are inconsistent with previous observations that ROS induced an increase in HO-1 expression via the PI3K/Akt signaling pathway in other cells type [56,57], which may be due to specific cell types or other factors. We cannot resolve this problem in the present study.…”

Involvement of CK2 in activation of electrophilic genes in endothelial cells by oxidized phospholipids

“…However, the mechanisms of activation are only partially understood. A candidate signaling molecule is PI3K, which is well characterized as an important mediator of biological activity of OxPLs ( 20,21 ) and, on the other hand, has been shown to play a critical role in the induction of NRF2 and NRF2-dependent genes in response to oxidative stressors and electrophilic compounds ( 7,(22)(23)(24). Based on these data, we asked whether PI3K plays a role in activation of electrophilic stress by OxPLs.…”

Amelioration of radiation-induced hematopoietic syndrome by an antioxidant chlorophyllin through increased stem cell activity and modulation of hematopoiesis

“…We had earlier shown that chlorophyllin enhanced the expression of antiapoptotic genes in the lymphocytes and thereby modulated lymphocyte homeostasis and immune responses in vivo [21]. Chlorophyllin has also been shown to activate the pro-survival transcription factor Nrf-2 in human umbilical vein endothelial cells and prevent oxidative stress induced apoptosis in vitro [35]. In the present investigations, it was revealed that chlorophyllin not only modulated the abundance and proliferation of HSPC but also enhanced the recovery from radiation induced bone marrow aplasia and lymphopenia.…”