Event Title

Presence of Sterol Response Element in Human Angiotensinogen Gene

Start Date

12-2-2010 12:00 AM

Description

Objective. The study was conducted to determine the sterol regulatory element binding protein (SREBP) regulatory element in human angiotensinogen (AGT) gene. Background. Excessive alcohol intake is linked to hypertension. The mechanism of alcoholmediated hypertension is unknown. Studies in hypertensive humans and transgenic animal models have established that plasma AGT level is the indicator of blood pressure. AGT is synthesized and secreted by liver. The plasma concentration of AGT is close to kd value of the enzymatic reaction between renin and AGT. Therefore, a rise in plasma AGT level can lead to a parallel increase in the level of angiotensin II (Ang II). Ang II is the vasoactive peptide involved in blood pressure regulation. Therefore, studying the regulation of AGT by liver during alcohol toxicity is important to understand the molecular mechanism of alcohol induced hypertension. Alcohol intake is known to activate sterol regulatory element binding protein (SREBP) in hepatocytes. Due to activation of SREBP in ethanol toxicity, the biosynthesis and secretion of AGT from liver may be increased if sterol response element(s) (SRE) in AGT is/are present. Methods. To define SRE element(s) in AGT, electrophoretic mobility shift assay (EMSA) was performed with possible SRE of AGT and consensus SRE and nuclear extract from hepatocytes (HepG2) grown in delipidiated serum and purified SREBP-1a from E.coli. Results. Our studies demonstrate the presence of SRE element in AGT gene. Conclusion. Increased biosynthesis and secretion of AGT is anticipated due to ethanol toxicity among binge and chronic alcohol abusers. Grants. None.

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Feb 12th, 12:00 AM

Presence of Sterol Response Element in Human Angiotensinogen Gene

Objective. The study was conducted to determine the sterol regulatory element binding protein (SREBP) regulatory element in human angiotensinogen (AGT) gene. Background. Excessive alcohol intake is linked to hypertension. The mechanism of alcoholmediated hypertension is unknown. Studies in hypertensive humans and transgenic animal models have established that plasma AGT level is the indicator of blood pressure. AGT is synthesized and secreted by liver. The plasma concentration of AGT is close to kd value of the enzymatic reaction between renin and AGT. Therefore, a rise in plasma AGT level can lead to a parallel increase in the level of angiotensin II (Ang II). Ang II is the vasoactive peptide involved in blood pressure regulation. Therefore, studying the regulation of AGT by liver during alcohol toxicity is important to understand the molecular mechanism of alcohol induced hypertension. Alcohol intake is known to activate sterol regulatory element binding protein (SREBP) in hepatocytes. Due to activation of SREBP in ethanol toxicity, the biosynthesis and secretion of AGT from liver may be increased if sterol response element(s) (SRE) in AGT is/are present. Methods. To define SRE element(s) in AGT, electrophoretic mobility shift assay (EMSA) was performed with possible SRE of AGT and consensus SRE and nuclear extract from hepatocytes (HepG2) grown in delipidiated serum and purified SREBP-1a from E.coli. Results. Our studies demonstrate the presence of SRE element in AGT gene. Conclusion. Increased biosynthesis and secretion of AGT is anticipated due to ethanol toxicity among binge and chronic alcohol abusers. Grants. None.