Dehydroepiandrosterone-Mediated Stimulation of Sigma-1 Receptor Activates Akt-eNOS Signaling in the Thoracic Aorta of Ovariectomized Rats with Abdominal Aortic Banding

被引:28
作者
Bhuiyan, Shenuarin [1 ]
Tagashira, Hideaki [1 ]
Fukunaga, Kohji [1 ]
机构
[1] Tohoku Univ, Dept Pharmacol, Grad Sch Pharmaceut Sci, Aoba Ku, Sendai, Miyagi 9808578, Japan
关键词
Dehydroepiandrosterone (DHEA); Endothelial nitric oxide synthase (eNOS); Myocardial hypertrophy; Protein kinase B (Akt); Sigma-1 receptor (Sig-1R); IMPROVES ENDOTHELIAL FUNCTION; ISCHEMIC-HEART-DISEASE; NITRIC-OXIDE SYNTHASE; LEFT-VENTRICULAR MASS; CELL-PROLIFERATION; PROTEIN-KINASE; IN-VITRO; PLASMA DEHYDROEPIANDROSTERONE; ORAL DEHYDROEPIANDROSTERONE; ENDOGENOUS ANDROGENS;
D O I
10.1111/j.1755-5922.2010.00196.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Decreased dehydroepiandrosterone (DHEA) levels are associated with endothelial dysfunction and increased cardiovascular mortality in postmenopausal women. Using ovariectomized rats, we first defined whether expression of sigma-1 receptor (Sig-1R) in the aorta is regulated following pressure overload (PO) and also after DHEA treatment. We also investigated effects of DHEA known as Sig-1R agonist on impaired Akt/endothelial nitric oxide synthase (eNOS) signaling in the thoracic aorta under PO. Research design/methods: Wistar rats subjected to bilateral ovariectomy (OVX) were further treated with abdominal aortic stenosis 2 weeks later. DHEA (15 and 30 mg/kg) was administered orally once a day for 14 days starting from 2 weeks after the aortic banding. Results: Time course study indicated that expression of Sig-1R expression and eNOS decreased time dependently in the thoracic aorta from 1 to 4 weeks after PO. DHEA treatment significantly inhibited the decreased Sig-1R expression in the thoracic aorta. The DHEA treatment also significantly restored PO-induced impaired Akt phosphorylation and stimulated eNOS protein expression with concomitant increased Akt-mediated eNOS phosphorylation (Ser1177). We did not find any changes in the phosphorylation of ERK1/2 and PKC alpha in the aorta following PO and after treatment with DHEA. Conclusion: We here reported, for the first time, that DHEA treatment induces the upregulation and stimulation of Sig-1R in the thoracic aorta that stimulate Sig-1R-mediated Akt-eNOS signaling pathways in ovariectomized rats under PO.
引用
收藏
页码:219 / 230
页数:12
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