Oxidative stress plays a permissive role in alpha 2-adrenoceptor-mediated events in immortalized SHR proximal tubular epithelial cells

• Type: Article in International Scientific Journal
• Date: 2008

Authors

Simao, S (Author) Other; Sonia Fraga (Author) FFUP; Jose, PA (Author) Other; soares-da-silva, p (Author) FMUP

Journal

Title: Molecular and Cellular Biochemistry

Vol. 315

Pages: 31-39

ISSN: 0300-8177

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 13 Citations

Scopus - 13 Citations

Other information

Authenticus ID: P-003-XH2

DOI: 10.1007/s11010-008-9785-6

Abstract (EN): The present study evaluated the role of oxidative stress on alpha(2)-adrenoceptor-mediated events (Cl(-)/HCO(3)(-) exchanger activity and cAMP accumulation) in immortalized renal proximal tubular epithelial (PTE) cells from the spontaneously hypertensive rat (SHR) and its normotensive control (Wistar Kyoto rat; WKY). The exposure of cells to alpha(2)-adrenoceptor agonist UK 14,304 reduced Cl(-)/HCO(3)(-) exchanger activity with EC(50) of 2.0 mu M in SHR PTE cells, whereas in WKY PTE cells no effects were observed. These effects were abolished by yohimbine, an alpha(2)-adrenoceptor antagonist, but insensitive to prazosin. Both forskolin and dibutyryl cAMP stimulated Cl(-)/HCO(3)(-) exchanger activity in WKY and SHR PTE cells, which was prevented by the PKA inhibitor H-89. Forskolin increased cAMP levels in both WKY and SHR PTE cells to a similar extent, but UK 14,304 significantly reduced the forskolin-induced increase in cAMP levels in only SHR PTE cells. Immunoblotting showed that expression of alpha(2B)-adrenoceptors was 12-times greater in SHR PTE cells than in WKY PTE cells. SHR PTE cells have increased levels of H(2)O(2) and overexpress type 2 NADPH oxidase (NOX2) and p22(phox) compared with WKY cells. In SHR PTE cells, the NADPH oxidase inhibitor apocynin reduced their increased ability to generate H(2)O(2) and abolished the inhibitory effects of UK 14,304 on Cl(-)/HCO(3)(-)exchanger activity and cAMP accumulation. It is concluded that differences between WKY and SHR PTE cells on their sensitivity to alpha(2)-adrenoceptor agonists correlate with the expression of alpha(2B)-adrenoceptors. The increased generation of H(2)O(2) amplifies the response downstream to alpha(2)-adrenoceptor activation in SHR PTE cells.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9