Department of Anatomy, Faculty of Medicine, Kuwait University, Kuwait.
Department of Anatomy, Faculty of Medicine, Kuwait University, Kuwait.
Eur J Pharmacol. 2021 Aug 5;904:174167. doi: 10.1016/j.ejphar.2021.174167. Epub 2021 May 8.
Microvascular changes and retinal degeneration precede diabetic retinopathy. Oxidative stress alters several intracellular signaling pathways, which form the basis of diabetic retinopathy. Many antioxidants have been investigated as possible preventive and therapeutic remedies for diabetic retinopathy. The current study investigated the modulatory effects of trans-resveratrol on streptozotocin-induced type 1 diabetes mediated changes in the transcription and levels of apoptosis-related proteins and mitogen-activated protein kinases (MAPKs) in the retinal pigment epithelium (RPE) of adult male dark Agouti rats. In control rats, 5 mg/kg/d trans-resveratrol administration for 30 days increased gene expressions of tumor suppressor protein 53, Bcl2-associated X protein, B-cell lymphoma-2 (Bcl2), Caspase-3 (CASP3), CASP8 and CASP9, p38αMAPK, c-Jun N-terminal kinase-1 (JNK1), and extracellular signal-regulated kinase-1 (ERK1). On the other hand, diabetes decreased gene expressions of CASP3, CASP8, p38αMAPK, JNK, and ERK1. Trans-resveratrol reversed the inhibited gene expressions of CASP8, p38αMAPK, JNK, and ERK1 to normal control levels in diabetic rats. Trans-resveratrol normalized diabetes-induced upregulation of CASP3 and -9, cytochrome-c, Bcl-2, and ERK1 proteins. In conclusion, Trans-resveratrol-induced alterations in gene expressions do not seem to affect RPE functions as they do not reflect as altered protein functions. Trans-resveratrol imparts its protective effects by normalizing apoptosis-related proteins and ERK1 but does not affect JNK proteins. Trans-resveratrol causes cytostasis in RPE of normal rats by upregulating Bcl2 protein and apoptotic proteins.
微血管变化和视网膜变性先于糖尿病视网膜病变。氧化应激改变了几种细胞内信号通路，这构成了糖尿病视网膜病变的基础。许多抗氧化剂已被研究作为糖尿病视网膜病变的可能预防和治疗方法。本研究调查了反式白藜芦醇对链脲佐菌素诱导的 1 型糖尿病介导的成年雄性深褐色 Agouti 大鼠视网膜色素上皮（RPE）中细胞凋亡相关蛋白和丝裂原活化蛋白激酶（MAPKs）转录和水平变化的调节作用。在对照大鼠中，30 天内每天给予 5mg/kg/d 的反式白藜芦醇可增加肿瘤抑制蛋白 53、Bcl2 相关 X 蛋白、B 细胞淋巴瘤-2（Bcl2）、Caspase-3（CASP3）、CASP8 和 CASP9、p38αMAPK、c-Jun N-末端激酶-1（JNK1）和细胞外信号调节激酶-1（ERK1）的基因表达。另一方面，糖尿病降低了 CASP3、CASP8、p38αMAPK、JNK 和 ERK1 的基因表达。反式白藜芦醇使糖尿病大鼠中受抑制的 CASP8、p38αMAPK、JNK 和 ERK1 的基因表达恢复到正常对照水平。反式白藜芦醇使糖尿病诱导的 CASP3 和 -9、细胞色素-c、Bcl-2 和 ERK1 蛋白的上调正常化。总之，反式白藜芦醇诱导的基因表达变化似乎不会影响 RPE 的功能，因为它们不会反映改变的蛋白质功能。反式白藜芦醇通过使与凋亡相关的蛋白和 ERK1 正常化而发挥其保护作用，但不影响 JNK 蛋白。反式白藜芦醇通过上调 Bcl2 蛋白和凋亡蛋白使正常大鼠的 RPE 产生细胞静止。
