Heme oxygenase-1 expression is down-regulated by angiotensin II and under hypertension in human neutrophils.
Angiotensin II (Ang II) is a peptide hormone able to elicit a strong production of reactive oxygen species by human neutrophils. In this work, we have addressed whether expression of heme oxygenase-1 (HO-1), an antioxidant enzyme, becomes altered in these cells upon Ang II treatment or under hypertension conditions. In neutrophils from healthy and hypertensive subjects, induction of HO-1 mRNA and protein expression with a parallel increase in enzyme activity took place upon treatment with 15-deoxy-Delta12,14-PGJ2 (15dPGJ2). However, Ang II prevented HO-1 synthesis by normal neutrophils in vitro, and HO-1 expression was depressed in neutrophils from hypertensive patients in comparison with cells from healthy subjects. In addition, Ang II treatment led to a reduced HO-1 enzyme activity to levels similar to those found in neutrophils from hypertensive patients. NO donors reversed the inhibition of 15dPGJ2-dependent HO-1 expression in neutrophils from hypertensive patients, and conversely, inhibition of inducible NO synthase (NOS2) activity counteracted the stimulatory effect of 15dPGJ2 on HO-1 expression in normal human neutrophils. Moreover, Ang II canceled 15dPGJ2-dependent induction of NOS2 mRNA synthesis. Present findings indicate that down-regulation of HO-1 expression in neutrophils from hypertensive subjects is likely exerted through the inhibition of NOS2 expression. Additionally, they underscore the potential usefulness of NO donors as new, therapeutic agents against hypertension.
Alba
Gonzalo
G
Departamento de Bioquímica Médica y Biología Molecular, Facultad de Medicina, Avda. Sánchez Pizjuán 4, Universidad de Sevilla, E-41009 Sevilla, Spain.
El Bekay
Rajaa
R
Chacón
Pedro
P
Reyes
M Edith
ME
Ramos
Eladio
E
Oliván
Josefina
J
Jiménez
Juan
J
López
José M
JM
Martín-Nieto
José
J
Pintado
Elízabeth
E
Sobrino
Francisco
F
D000804:Angiotensin II / Q000494:pharmacology*; D018929:Cell Culture Techniques; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology; D012016:Reference Values
C477819:15-deoxyprostaglandin J2; D000804:Angiotensin II; D052247:Nitric Oxide Synthase Type II; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D015230:Prostaglandin D2