Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia.
Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia.
Nutrients. 2023 Jul 5;15(13):3036. doi: 10.3390/nu15133036.
Multiple alcohol use disorder (AUD)-related behavioral alterations are governed by protein kinase C epsilon (PKCε), particularly in the amygdala. Protein kinase C (PKC) is readily phosphorylated at Ser729 before activation by the mTORC2 protein complex. In keeping with this, the current study was conducted to assess the variations in mTORC2 and PKCε during different ethanol exposure stages. The following groups of rats were employed: control, acute, chronic, ethanol withdrawal (EW), and EW + ethanol (EtOH). Ethanol-containing and non-ethanol-containing modified liquid diets (MLDs) were administered for 27 days. On day 28, either saline or ethanol (2.5 g/kg, 20% /) was intraperitoneally administered, followed by bilateral amygdala extraction. PKCε mRNA levels were noticeably increased in the amygdala of the EW + EtOH and EW groups. Following chronic ethanol consumption, the stress-activated map kinase-interacting protein 1 (Sin1) gene expression was markedly decreased. In the EW, EW + EtOH, and chronic ethanol groups, there was a profound increase in the protein expression of mTOR, Sin1, PKCε, and phosphorylated PKCε (Ser729). The PKCε gene and protein expressions showed a statistically significant moderate association, according to a correlation analysis. Our results suggest that an elevated PKCε protein expression in the amygdala during EW and EW + EtOH occurred at the transcriptional level. However, an elevation in the PKCε protein expression, but not its mRNA, after chronic ethanol intake warrants further investigation to fully understand the signaling pathways during different episodes of AUD.
多种酒精使用障碍（AUD）相关的行为改变受蛋白激酶 C ɛ（PKCε）调控，尤其是在杏仁核中。蛋白激酶 C（PKC）在被 mTORC2 蛋白复合物激活之前，可迅速在丝氨酸 729 位磷酸化。基于此，本研究旨在评估不同乙醇暴露阶段时 mTORC2 和 PKCε 的变化。本研究使用了以下大鼠组：对照组、急性组、慢性组、乙醇戒断（EW）组和 EW+乙醇（EtOH）组。大鼠接受含乙醇和不含乙醇的改良液体饮食（MLD）喂养 27 天。第 28 天，大鼠腹腔内注射生理盐水或乙醇（2.5 g/kg，20%/），然后提取双侧杏仁核。在 EW+EtOH 和 EW 组中，杏仁核中的 PKCε mRNA 水平明显增加。在慢性乙醇消耗后，应激激活的 MAP 激酶相互作用蛋白 1（Sin1）基因表达明显降低。在 EW、EW+EtOH 和慢性乙醇组中，mTOR、Sin1、PKCε 和磷酸化 PKCε（Ser729）的蛋白表达显著增加。根据相关性分析，PKCε 基因和蛋白表达呈中度关联。我们的结果表明，在 EW 和 EW+EtOH 期间，杏仁核中 PKCε 蛋白表达的增加发生在转录水平上。然而，慢性乙醇摄入后 PKCε 蛋白表达的增加而不是其 mRNA 的增加需要进一步研究，以充分了解 AUD 不同发作期间的信号通路。
