The environmental toxicant lead (Pb) and the essential element calcium (Ca) play an interactive role in extracellular and intracellular regulatory functions that affect health. Lead’s usurping calcium binding sites, as well as its interactions with thiols and phosphates have been suggested to be the basis for adverse effects on many organ systems especially the nervous system. Among regulatory processes controlled by Ca are calmodulin-dependent phosphodiesterase, calmodulin-dependent protein kinases, calmodulin inhibitor sensitive potassium channels, and calmodulin-independent protein kinase C (PKC) activation. This review focused on Pb studies describing the modulation of PKC, which is also regulated by steroids. Steroid hormone regulation may relate to a focal point for the sex differences of Pb and cellular signaling events. Picomolar concentrations of Pb may stimulate partially purified PKC, but higher concentrations inhibit activity. Although knowledge exists regarding Pb and PKC isoforms, especially interaction of Pb with the purified enzyme, there are conflicting reports concerning metal-mediated activation or inhibition of PKC and downstream signaling events. The effect of Pb on PKC in vivo remains elusive. Most reports of Pb and PKC in whole animal and human studies indicated that Pb either inhibits PKC or exerts no significant effect. However, most of the animal studies were performed with males. Recent studies performed with females and males separately revealed that females and males respond to Pb quite differently, and for this reason, it is suggested that future Pb studies of PKC and other biomedical investigations be performed with females and males.

环境毒物铅（Pb）和必需元素钙（Ca）在影响健康的细胞外和细胞内调节功能中起着相互作用的作用。铅的篡改钙结合位点以及与硫醇和磷酸盐的相互作用已被认为是对许多器官系统特别是神经系统产生不利影响的基础。Ca控制的调节过程包括钙调蛋白依赖性磷酸二酯酶，钙调蛋白依赖性蛋白激酶，钙调节蛋白抑制剂敏感性钾通道和钙调蛋白依赖性蛋白激酶C（PKC）活化。这篇综述集中在描述PKC调节的Pb研究中，PKC也受类固醇调节。类固醇激素调节可能与Pb性别差异和细胞信号转导事件有关。皮摩尔浓度的Pb可能会刺激部分纯化的PKC，但较高的浓度会抑制活性。尽管存在有关Pb和PKC同工型的知识，尤其是Pb与纯化酶的相互作用，但有关金属介导的PKC激活或抑制以及下游信号传导事件的报道相互矛盾。铅对PKC的影响体内仍然难以捉摸。在整个动物和人类研究中，大多数有关Pb和PKC的报道都表明Pb抑制PKC或不发挥明显作用。但是，大多数动物研究都是对雄性进行的。最近对雌性和雄性进行的研究分别表明，雌性和雄性对Pb的反应差异很大，因此，建议对雌性和雄性进行将来的PKC的Pb研究和其他生物医学研究。