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正常和病理性人类睾丸均表达激素敏感性脂肪酶以及脂质受体CLA-1/SR-BI和CD36。

Normal and pathological human testes express hormone-sensitive lipase and the lipid receptors CLA-1/SR-BI and CD36.

作者信息

Arenas Maria I, Lobo Maria V T, Caso Enrique, Huerta Lidia, Paniagua Ricardo, Martín-Hidalgo Martin A

机构信息

Department of Cell Biology and Genetics, University of Alcalá, Alcalá de Henares, Madrid, Spain.

出版信息

Hum Pathol. 2004 Jan;35(1):34-42. doi: 10.1016/j.humpath.2003.08.015.

Abstract

Numerous studies have demonstrated the important role of cholesterol and cholesteryl esters in tumor cell proliferation and progression of cancer. However, few studies have focused on the role of lipid transporters and lipases in cancer development and progression. The present study examined the expression of hormone-sensitive lipase (HSL) and the scavenger receptors CLA-1/SR-BI and CD36 in normal human testis and in nontumor and tumor testicular disorders by immunohistochemistry and Western blotting analysis. In normal young testes, immunoreaction to CLA-1/SR-BI was found in the spermatid acrosomic vesicle and on the surface of Sertoli and Leydig cells. HSL was detected in spermatogonia, the Golgi region of spermatocytes, the nucleus of spermatids, and the cytoplasm of both Sertoli and Leydig cells. Elderly testes and testes with hypospermatogenesis showed a similar staining pattern to that of normal young testes except for CD36, which was expressed in Sertoli cells. Cryptorchid testes demonstrated intense labeling to HSL and weak labeling to SR-BI in Sertoli cells (nucleus and cytoplasm) and Leydig cells (cytoplasm). Seminiferous tubules with intratubular germ cell neoplasia exhibited intense immunolabeling to the 3 lipid receptors in the surface of neoplastic cells and to HSL in the nucleus. In seminoma and spermatocytic seminoma, neoplastic cells labeled to HSL but failed to stain with antilipid receptors; in the seminiferous tubules at the periphery of the tumour, Charcot-Böttcher crystalloids of Sertoli cells were strongly positive to CLA-1. Testes with mature teratoma showed a weak reaction to CD36 and SR-BI in some cells of enteric-type glands, and immature teratoma were exclusively immunolabeled with HSL. Western blotting analysis revealed that multiple bands were immunolabeled, with differences seen between normal and pathological testes. The results of this study indicate that the presence of lipid receptors (CLA-1/SR-BI) and hormone-sensitive lipase in Leydig cells suggests a role of these proteins in steroidogenesis. Also, these proteins seem to be involved in spermiogenesis, as their labeling in spermatids suggests. In nonmalignant and malignant pathologies, cholesterol metabolism is probably altered, and HSL labeling in neoplastic germ cell nuclei suggests a still-unknown function of this enzyme, probably related to cell cycle regulation.

摘要

众多研究已证明胆固醇及胆固醇酯在肿瘤细胞增殖和癌症进展中发挥的重要作用。然而,很少有研究关注脂质转运蛋白和脂肪酶在癌症发生及进展中的作用。本研究通过免疫组织化学和蛋白质印迹分析,检测了激素敏感性脂肪酶(HSL)、清道夫受体CLA-1/SR-BI和CD36在正常人类睾丸以及非肿瘤性和肿瘤性睾丸疾病中的表达情况。在正常年轻睾丸中,在精子细胞顶体小泡以及支持细胞和间质细胞表面发现了对CLA-1/SR-BI的免疫反应。在精原细胞、精母细胞的高尔基体区域、精子细胞核以及支持细胞和间质细胞的细胞质中检测到了HSL。老年睾丸和精子发生低下的睾丸除了支持细胞中表达的CD36外,显示出与正常年轻睾丸相似的染色模式。隐睾症患者的支持细胞(细胞核和细胞质)和间质细胞(细胞质)中,HSL呈现强标记,SR-BI呈现弱标记。伴有管内生殖细胞瘤变的生精小管在肿瘤细胞表面对这三种脂质受体以及细胞核中的HSL均呈现强免疫标记。在精原细胞瘤和精母细胞性精原细胞瘤中,肿瘤细胞标记为HSL,但未被抗脂质受体染色;在肿瘤周边的生精小管中,支持细胞的夏科-博歇结晶对CLA-1呈强阳性。成熟畸胎瘤的睾丸在肠型腺体的一些细胞中对CD36和SR-BI呈弱反应,而未成熟畸胎瘤仅用HSL进行免疫标记。蛋白质印迹分析显示有多个条带被免疫标记,正常睾丸和病理睾丸之间存在差异。本研究结果表明,间质细胞中脂质受体(CLA-1/SR-BI)和激素敏感性脂肪酶的存在表明这些蛋白质在类固醇生成中发挥作用。此外,这些蛋白质似乎参与了精子形成过程,正如它们在精子细胞中的标记所示。在非恶性和恶性病变中,胆固醇代谢可能发生改变,肿瘤性生殖细胞核中的HSL标记表明该酶可能具有与细胞周期调节相关的未知功能。

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