Document Type

Article

Publication Date

2014

Abstract

Prostate cancer is diagnosed in over 186,000 men in the United States and accounts for more than 28,000 deaths annually. Angiotensin II (AngII) is a major effector peptide of the renin-angiotensin system (RAS), and is an important factor in hypertension. Correlations between ACE therapy and improved prostate cancer outcomes led to in vitro studies the action of AngII in cultured prostate cancer cell lines. Investigators have reported that exogenous application of Ang II to LNCaP cells results in the activation of Akt signaling, increased activity of SOD, and glutathione peroxidase. As the mitochondrion is a major contributor of total cellular ROS, we investigated the effect of AngII on mitochondrial respiratory function directly. AngII can bind to either of two receptors: the losartan-sensitive AT1-R and the PD123319-sensitive AT2-R. We present Western-blot evidence of the presence of AT1-R at the plasma membrane and both AT1-R and AT2-R receptor at the mitochondrion in LNCaP cells. Using fluorescent respirometry, we show AngII stimulates LNCaP whole-cell respiration over a 24-hour period with maximal stimulation at 5 hours post-application. Increased respiratory rates are abolished using either losartan or PD123319 at time points up to 5 hours post-application implicating the participation of both receptor subtypes in mediating this effect. At 24 hours post-application respiratory rates remain elevated, though to a lesser degree, and appear to be sustained by AT1-R activity only. Given the differential contribution of these two receptor sub-types to modulation in respiratory activity, there may be two independent pathways activated by their respective AT-R subtype.

Comments

Originally published in:

The FASEB Journal, Volume 28, Issue S1, 1159.1. 01 April 2014

DOI: https://doi.org/10.1096/fasebj.28.1_supplement.1159.11

Download

Included in

Biology Commons

Share

COinS