Angiotensin II induces oxidative stress and upregulates neuroprotective signaling from the NRF2 and KLF9 pathway in dopaminergic cells

The intracellular renin-angiotensin system: Friend or foe. Some light from the dopaminergic neurons

“…In addition to the above-mentioned mechanisms, other cell protective mechanisms compensate the possible deleterious effects of the activation of the pro-oxidative Ang II/ AT1 arm. In dopaminergic neurons, we have recently observed that Ang II, alone or combined with other pro-oxidative factors, activates the transcription factor NRF2 (i.e., NFE2L2, nuclear factor- erythroid 2 related factor 2) pathway ( Parga et al, 2018 ). NRF2 is a key regulator of cell antioxidant mechanisms and redox homeostasis.…”

“…Consistent with this, activation of the NRF2 pathway has shown neuroprotective properties in dopaminergic neurons by regulation of the expression of antioxidant enzymes and other transcription factors, such as KLF9, which reduce oxidative stress both in vitro and in vivo. The release of superoxide from the AT1/Nox2 pathway induces NRF2 activation ( Parga et al, 2018 ). However, AT1 receptor activation may promote NRF2 pathway via alternative mechanisms such as ERK1/2 ( Huang et al, 1996 ) and PKC ( Huang et al, 2000 ), as phosphorylation of NRF2 by these kinases promote the dissociation from the inhibitor KEAP1 and nuclear localization of NRF2 ( Xu et al, 2006 ).…”

Sulforaphane-Induced Klf9/Prdx6 Axis Acts as a Molecular Switch to Control Redox Signaling and Determines Fate of Cells

“…With mild to moderate or high levels of oxidative stress or with use of Nrf2 inducers, Nrf2-Keap1 interaction is disrupted and Nrf2 is accumulated in nucleus in a dose-dependent manner [1]. However, under excessive oxidative stress, the excessive nuclear Nrf2 binds to the regulatory region of Kruppel-like factor 9 ( Klf9 ) gene promoter and transactivates its expression, which suppresses some of the antioxidant genes by binding to their repressive sites (5′-C A/G CCC-3′) [26,31] and causes cellular injury [32].…”

Data on the effect of Angiotensin II and 6-hydroxydopamine on reactive oxygen species production, antioxidant gene expression and viability of different neuronal cell lines

“…Data are represented as mean absorbance relative to control ± SEM. Values of MTT absorbance of Mes23.5 cells that have not been infected (No vector) from [1] were also included as a reference. * p < 0.001 vs control.…”

“…We provide data that NRF2 overexpression increases cell viability in response to oxidative stress inducers compared to control cells, and that these inducers can, both separately and in combination, enhance the expression of NRF2-regulated genes heme oxygenase 1 (Hmox1), NAD(P)H quinone dehydrogenase 1 (Nqo1) and Kruppel like factor 9 (Klf9). Interpretation of these data and additional information is presented in the research article “Angiotensin II induces oxidative stress and upregulates neuroprotective signaling from the NRF2 and KLF9 pathway in dopaminergic cells“ (Parga et al, 2018) [1] .…”