Mechanism Of Transcriptional Factors Nrf1 And/or Nrf2 In Cellular Stress Response,with Identification Of Biochemical Characteristics In Nrf1D

The stress response of eukaryotic evolution is beneficial for maintaining cell homeostasis and responding to external stimulation.Finding the regulatory mechanism to stress response is of great significance for preventing,alleviating and even curing diseases related to severe stress response.The transcription factor Nrf1 plays an important role in maintaining cell homeostasis and the growth of the organism throughout the life,the transcription factor Nrf2 plays an extremely important role in regulating the homeostatic redox homeostasis,involving all aspects of cell life activities,the two are structurally similar and their functions overlap.However,the structure of Nrf1 mutant Nrf1 D is similar to Nrf1,but its unique C-terminal faces the transmembrane region inside the endoplasmic reticulum lumen,making it tighter than Nrf1 in combining with the endoplasmic reticulum membrane.In order to understand the relationship between Nrf1,Nrf2 and stress response as well as the biochemical characteristics of Nrf1 D,this paper preliminarily explored when the cells induced by DTT and simulated cellular oxidative stress and endoplasmic reticulum stress environment,then used qPCR and Western Blot to detect the differential effects of Nrf1 and Nrf2 on cellular oxidative stress gene and endoplasmic reticulum stress gene.And the paper explored whether Nrf1 D has different functions due to its unique structure.The following conclusions were obtained:(1)Under the stimulation of DTT,there is an up-regulation in the expression of Nrf1 and Nrf2,the changes in Nrf1 transcription level and translational level may be collective effect of DTT stimulation and the stress response;(2)Nrf1 and Nrf2 differentially regulate the expression levels of oxidative stress and endoplasmic reticulum stress-related genes,among which Nrf1 plays a more prominent role in the regulation of cell homeostasis,while the function of Nrf2 is more focused on the regulation of stress response genes;(3)Nrf1D subtypes are present in multiple tissues of mice including plasma.85 kDa active proteins of Nrf1 D is less in the nucleus,most of which are present in the cytoplasm;(4)Nrf1D is more stable than Nrf1,which is partially protected by a unique TMc-related membrane to resist the degradation of intracellular proteasome,and its TMc region has a processing modification effect on Nrf1 D.In summary,Nrf1 and Nrf2 have synergistic effects in regulating oxidative stress and endoplasmic reticulum stress genes.Nrf1 D is widely present in mice tissues and found to be abundant in plasma,thus it is presumed that Nrf1 D reach plasma through a potential secretory pathway.However,this study is only a preliminary analysis of the structural characteristics of Nrf1 D,providing a meaningful basis for further exploration of its unique features.