Berridge Michael J
The Babraham Institute, Babraham, Cambridge CB22 3AT, United Kingdom.
Biochem Biophys Res Commun. 2015 Apr 24;460(1):53-71. doi: 10.1016/j.bbrc.2015.01.008.
Vitamin D deficiency has been linked to many human diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), hypertension and cardiovascular disease. A Vitamin D phenotypic stability hypothesis, which is developed in this review, attempts to describe how this vital hormone acts to maintain healthy cellular functions. This role of Vitamin D as a guardian of phenotypic stability seems to depend on its ability to maintain the redox and Ca(2+) signalling systems. It is argued that its primary action is to maintain the expression of those signalling components responsible for stabilizing the low resting state of these two signalling pathways. This phenotypic stability role is facilitated through the ability of vitamin D to increase the expression of both Nrf2 and the anti-ageing protein Klotho, which are also major regulators of Ca(2+) and redox signalling. A decline in Vitamin D levels will lead to a decline in the stability of this regulatory signalling network and may account for why so many of the major diseases in man, which have been linked to vitamin D deficiency, are associated with a dysregulation in both ROS and Ca(2+) signalling.
维生素D缺乏与许多人类疾病有关，如阿尔茨海默病（AD）、帕金森病（PD）、多发性硬化症（MS）、高血压和心血管疾病。本综述中提出的维生素D表型稳定性假说，试图描述这种重要激素如何维持健康的细胞功能。维生素D作为表型稳定性守护者的这一作用，似乎取决于其维持氧化还原和Ca(2+)信号系统的能力。有人认为，其主要作用是维持那些负责稳定这两种信号通路低静息状态的信号成分的表达。维生素D增加Nrf2和抗衰老蛋白Klotho表达的能力促进了这种表型稳定性作用，而Nrf2和Klotho也是Ca(2+)和氧化还原信号的主要调节因子。维生素D水平的下降将导致这种调节信号网络稳定性的下降，这可能解释了为什么许多与维生素D缺乏有关的人类主要疾病都与ROS和Ca(2+)信号失调有关。
