Roy Nivedita, Chakraborty Supriya, Paul Chowdhury Bidisha, Banerjee Sayantan, Halder Kuntal, Majumder Saikat, Majumdar Subrata, Sen Parimal C
Division of Molecular Medicine, Bose Institute, Kolkata, West Bengal, India.
PLoS One. 2014 Oct 17;9(10):e110843. doi: 10.1371/journal.pone.0110843. eCollection 2014.
Calcium is an ubiquitous cellular signaling molecule that controls a variety of cellular processes and is strictly maintained in the cellular compartments by the coordination of various Ca2+ pumps and channels. Two such fundamental calcium pumps are plasma membrane calcium ATPase (PMCA) and Sarco/endoplasmic reticulum calcium ATPase (SERCA) which play a pivotal role in maintaining intracellular calcium homeostasis. This intracellular Ca2+ homeostasis is often disturbed by the protozoan parasite Leishmania donovani, the causative organism of visceral leishmaniasis. In the present study we have dileneated the involvement of PMCA4 and SERCA3 during leishmaniasis. We have observed that during leishmaniasis, intracellular Ca2+ concentration was up-regulated and was further controlled by both PMCA4 and SERCA3. Inhibition of these two Ca2+-ATPases resulted in decreased parasite burden within the host macrophages due to enhanced intracellular Ca2+. Contrastingly, on the other hand, activation of PMCA4 was found to enhance the parasite burden. Our findings also highlighted the importance of Ca2+ in the modulation of cytokine balance during leishmaniasis. These results thus cumulatively suggests that these two Ca2+-ATPases play prominent roles during visceral leishmaniasis.
钙是一种普遍存在的细胞信号分子，可控制多种细胞过程，并通过各种Ca2+泵和通道的协同作用严格维持在细胞区室中。两种这样的基本钙泵是质膜钙ATP酶（PMCA）和肌浆网/内质网钙ATP酶（SERCA），它们在维持细胞内钙稳态中起关键作用。这种细胞内Ca2+稳态常常受到内脏利什曼病的病原体——原生动物寄生虫杜氏利什曼原虫的干扰。在本研究中，我们阐述了PMCA4和SERCA3在利什曼病中的作用。我们观察到，在利什曼病期间，细胞内Ca2+浓度上调，并进一步受到PMCA4和SERCA3的控制。抑制这两种Ca2+ - ATP酶会因细胞内Ca2+增加而导致宿主巨噬细胞内的寄生虫负担减轻。相反，另一方面，发现激活PMCA4会增加寄生虫负担。我们的研究结果还突出了Ca2+在利什曼病期间调节细胞因子平衡中的重要性。因此，这些结果累积表明这两种Ca2+ - ATP酶在内脏利什曼病中起重要作用。
