title: Oxidative stress increases angiotensin receptor type I responsiveness by increasing receptor degree of aggregation using image correlation spectroscopy.
abstract: Oxidative stress and hyper-functioning of angiotensin II receptor type I (AT(1)R) are commonly observed in hypertensive patients but the relationship between oxidative stress and AT(1)R function is still unclear. We investigated the effects of H(2)O(2) treatment on AT(1)R-mediated intracellular calcium [Ca(2+)](i) signaling and its cell surface distribution pattern in HEK cells stably expressing EGFP-tagged rat AT(1)R using image correlation spectroscopy (ICS). Following H(2)O(2) treatment (50-800μM), [Ca(2+)](i) was significantly increased upon angiotensin II stimulation. Similarly ICS revealed a significant increase in degree of AT(1)R aggregation in H(2)O(2) treated group during Ang II activation but no difference in cluster density compared with untreated control cells or those with N-acetyl cysteine pretreatment. Thus, oxidative stress-induced AT(1)R hyper-responsiveness can be attributed by an increase in cell surface receptor aggregation state, possibly stemming in part from oxidant-related increase receptor-receptor interactions.
authors.affiliation: Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
authors.forename: Titiwat
authors.initials: T
authors.lastname: Sungkaworn
authors.forename: Yongwimon
authors.initials: Y
authors.lastname: Lenbury
authors.forename: Varanuj
authors.initials: V
authors.lastname: Chatsudthipong
mesh_terms: D002460:Cell Line; D006801:Humans; D018384:Oxidative Stress; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D013057:Spectrum Analysis / Q000379:methods*
chemical_list: D044140:Receptor, Angiotensin, Type 1