Human Angiotensinogen Gene Regulation by Hypoxia Inducible Factor - A Cell-Based Study
Abstract
Alcohol usage is linked to increased blood pressure and fibrotic transformation of the liver after the hepatocyte death. Angiotensinogen (AGT) is the source of Ang II which is produced from AGT by sequential action of renin followed by angiotensin converting enzyme. The blood AGT levels correlate to blood pressure, therefore, an increase in blood AGT levels result into corresponding increase in Ang II levels affecting blood pressure regulation and liver fibrogenic processes. Alcohol metabolism by the liver produces oxidative stress (ROS) that activates hypoxia inducible transcription factor-1alpha (HIF1α). Hepatocytes lose alcohol metabolizing enzymes after passages, therefore HIF-1α mediated activation of AGT gene was studied by treatment with hypoxia mimetics on AGT secretion by hepatocytes. It was observed that AGT secretion levels were increased with HepG2 and Huh7 hepatocytes after deferoxamine (60nM and 120 nM) and cobalt chloride (10mM and 20mM) post fourand six-hours treatments. The increased secretion of AGT was sustained till 24 hrs. by HepG2 cells followed by decreased secretion at 48 hrs. as compare to control. The cellular level of AGT were also increased till 24 hrs. followed by a decrease at 48 hrs. by HepG2 cells. The presence of hypoxia response element(s) (HREs; RCGTG) in hAGT -10.0 kb promoter was analyzed using ApoE program and a total of 13 HREs were found. It is likely that hypoxia mimetics increase angiotensinogen secretion through HREs and these HREs may cause increased AGT secretion from hepatocytes after ethanol exposure and other hypoxic conditions such as tumors environment.
Faculty Sponsors
Dr. Emily Schmitt Lavin, Dr. Rais Ansari
Project Type
Event
Location
Alvin Shermany Library
Start Date
4-5-2019 1:00 PM
End Date
4-5-2019 5:00 PM
Human Angiotensinogen Gene Regulation by Hypoxia Inducible Factor - A Cell-Based Study
Alvin Shermany Library
Alcohol usage is linked to increased blood pressure and fibrotic transformation of the liver after the hepatocyte death. Angiotensinogen (AGT) is the source of Ang II which is produced from AGT by sequential action of renin followed by angiotensin converting enzyme. The blood AGT levels correlate to blood pressure, therefore, an increase in blood AGT levels result into corresponding increase in Ang II levels affecting blood pressure regulation and liver fibrogenic processes. Alcohol metabolism by the liver produces oxidative stress (ROS) that activates hypoxia inducible transcription factor-1alpha (HIF1α). Hepatocytes lose alcohol metabolizing enzymes after passages, therefore HIF-1α mediated activation of AGT gene was studied by treatment with hypoxia mimetics on AGT secretion by hepatocytes. It was observed that AGT secretion levels were increased with HepG2 and Huh7 hepatocytes after deferoxamine (60nM and 120 nM) and cobalt chloride (10mM and 20mM) post fourand six-hours treatments. The increased secretion of AGT was sustained till 24 hrs. by HepG2 cells followed by decreased secretion at 48 hrs. as compare to control. The cellular level of AGT were also increased till 24 hrs. followed by a decrease at 48 hrs. by HepG2 cells. The presence of hypoxia response element(s) (HREs; RCGTG) in hAGT -10.0 kb promoter was analyzed using ApoE program and a total of 13 HREs were found. It is likely that hypoxia mimetics increase angiotensinogen secretion through HREs and these HREs may cause increased AGT secretion from hepatocytes after ethanol exposure and other hypoxic conditions such as tumors environment.
