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首页> 外文期刊>American Journal of Physiology >Gender-related distinctions in protein kinase C activity in rat vascular smooth muscle.
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Gender-related distinctions in protein kinase C activity in rat vascular smooth muscle.

机译：大鼠血管平滑肌中蛋白激酶C活性的性别相关区分。

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摘要

Gender differences in vascular reactivity have been suggested; however, the cellular mechanisms involved are unclear. We tested the hypothesis that the gender differences in vascular reactivity reflect gender-related, possibly estrogen-mediated, distinctions in the expression and activity of specific protein kinase C (PKC) isoforms in vascular smooth muscle. Aortic strips were isolated from intact and gonadectomized male and female Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Isometric contraction was measured in endothelium-denuded aortic strips. PKC activity was measured in the cytosolic and particulate fractions, and the amount of PKC was measured using Western blots and isoform-specific anti-PKC antibodies. In intact male WKY rats, phenylephrine (Phe, 10(-5) M) and phorbol 12,13-dibutyrate (PDBu, 10(-6) M) stimulated contraction to 0.37 +/- 0.02 and 0.42 +/- 0.02 g/mg tissue wt, respectively. The basal particulate/cytosolic PKC activity ratio was 0.86 +/- 0.06, and Western blots revealed alpha-, delta-, and zeta-PKC isoforms. Phe and PDBu increased PKC activity and caused significant translocation of alpha- and delta-PKC from the cytosolic to particulate fraction. In intact female WKY rats, basal PKC activity, the amount of alpha-, delta-, and zeta-PKC, the Phe- and PDBu-induced contraction, and PKC activity and translocation of alpha- and delta-PKC were significantly reduced compared with intact male WKY rats. The basal PKC activity, the amount of alpha-, delta-, and zeta-PKC, the Phe and PDBu contraction, and PKC activity and alpha- and delta-PKC translocation were greater in SHR than WKY rats. The reduction in Phe and PDBu contraction and PKC activity in intact females compared with intact males was greater in SHR ( approximately 30%) than WKY rats ( approximately 20%). Phe and PDBu contraction and PKC activity were not significantly different between castrated males and intact males but were greater in ovariectomized (OVX) females than intact females. Treatment of OVX females or castrated males with 17 beta-estradiol, but not 17 alpha-estradiol, subcutaneous implants caused significant reduction in Phe and PDBu contraction and PKC activity that was greater in SHR than WKY rats. Phe and PDBu contraction and PKC activity in OVX females or castrated males treated with 17 beta-estradiol plus the estrogen receptor antagonist ICI-182,780 were not significantly different from untreated OVX females or castrated males. Thus a gender-related reduction in vascular smooth muscle contraction in female WKY rats with intact gonads compared with males is associated with reduction in the expression and activity of vascular alpha-, delta-, and zeta-PKC. The gender differences in vascular smooth muscle contraction and PKC activity are augmented in the SHR and are possibly mediated by estrogen.
机译：已经提出了血管反应性的性别差异。但是，涉及的细胞机制尚不清楚。我们检验了以下假设，即血管反应性中的性别差异反映了血管平滑肌中特定蛋白激酶C（PKC）亚型的表达和活性中与性别相关的，可能是雌激素介导的差异。从完整的和经性腺切除的雄性和雌性Wistar-Kyoto（WKY）大鼠和自发性高血压大鼠（SHR）中分离主动脉带。在内皮剥除的主动脉条中测量等距收缩。在胞浆和颗粒级分中测量PKC活性，并使用Western印迹和同工型特异性抗PKC抗体测量PKC的量。在完整的雄性WKY大鼠中，去氧肾上腺素（Phe，10（-5）M）和佛波12,13-二丁酸酯（PDBu，10（-6）M）刺激收缩至0.37 +/- 0.02和0.42 +/- 0.02 g /毫克组织重量，分别。基础颗粒/胞质PKC活性比为0.86 +/- 0.06，Western印迹显示α-，δ-和ζ-PKC同工型。 Phe和PDBu增加了PKC活性，并导致α-和δ-PKC从胞浆到颗粒级分的明显移位。在完整雌性WKY大鼠中，基础PKC活性，α-，δ-和zeta-PKC的量，Phe-和PDBu诱导的收缩以及PKC活性以及α-和δ-PKC的移位明显低于完整的雄性WKY大鼠。与WKY大鼠相比，SHR中的基础PKC活性，α-，δ-和zeta-PKC的量，Phe和PDBu的收缩，PKC活性以及α-和δ-PKC的移位更大。与完整雄性相比，完整雌性中Phe和PDBu收缩以及PKC活性的降低在SHR中（约30％）比WKY大鼠（约20％）更大。去势雄性和完整雄性之间的Phe和PDBu收缩和PKC活性无显着差异，但去卵巢（OVX）雌性中Phe和PDBu的收缩性比完整雌性中的更大。用17β-雌二醇而不是17α-雌二醇对OVX雌性或去势雄性进行治疗，皮下植入物引起Phe和PDBu收缩以及PKC活性的显着降低，在SHR中比WKY大鼠更大。用17β-雌二醇加雌激素受体拮抗剂ICI-182,780治疗的OVX女性或去势男性的Phe和PDBu收缩以及PKC活性与未治疗的OVX女性或去势男性无明显差异。因此，与雄性相比，雌性性腺完整的雌性WKY大鼠的血管平滑肌收缩的性别相关减少与血管α-，δ-和zeta-PKC的表达和活性降低有关。在SHR中，血管平滑肌收缩和PKC活性的性别差异增加，可能由雌激素介​​导。

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