Bcl-2是Bcl-2家族的重要成員之一。眾所周知它是一個的抗凋亡蛋白。Bcl-2可以透過與IP3R結合來調節細胞內鈣訊號傳導。它可以透過與IP3R結合來減少粒線體攝取，導致ER釋放到粒線體的鈣離子減少，從而降低細胞凋亡。鈣離子是細胞中重要的第二信使。其訊號傳導調節細胞內細胞的分化、運動、增殖和凋亡。對於Bcl-2與鈣的關係，每個人的研究都有不同的看法。在這項研究中，我們發現Bcl-2透過上調細胞膜上的鈣離子通道蛋白並引起鈣振盪來減少細胞凋亡。首先，我們觀察到Bcl-2的過度表現會導致細胞中自主鈣振盪。深入研究我們發現Bcl-2透過上調PMCA、NCX1、ORAI1、STIM1等細胞膜鈣離子通道，誘導鈣振盪來調節細胞內鈣水平，防止細胞凋亡。這個情形PMCA和NCX1尤其明顯，因為它們是負責將鈣離子直接轉運出細胞的通道蛋白。為了證明Bcl-2誘導的鈣振盪與PMCA以及NCX1之間的關聯，我們使用這兩種抑制劑（RES和ORM-10103）進行了研究。結果顯示，在抑制劑處理下，Bcl-2引發的鈣振盪顯著減少甚至消失，尤其是在PMCA中，顯示PMCA和NCX1確實在Bcl-2避免凋亡的機制中發揮重要作用。這是與先前研究截然不同的發現。然而，Bcl-2影響PMCA和NCX1等鈣通道的機制可能是未來需要進一步研究的議題。總之，我們的研究表明，Bcl-2透過調節鈣離子跨細胞膜的運輸，形成鈣振蕩來防止細胞死亡。這為未來的研究提供了新的方向。

Bcl-2 is one of the important members of the Bcl-2 family. It is well known as an anti-apoptotic protein. Bcl-2 can regulate intracellular calcium signaling by binding to IP3R. It can reduce mitochondrial calcium uptake by binding to IP3R, leading to a decrease in ER calcium release into the mitochondria, thereby achieving a reduction in cellular apoptosis. Calcium is an important second messenger in cells. Its signaling regulates intracellular cell differentiation, movement, proliferation and apoptosis. As for the relationship between Bcl-2 and calcium, everyone has different opinions in research. In this study, we found that Bcl-2 reduces cell apoptosis by upregulating calcium channel proteins on the cell membrane and causing calcium oscillation. First, we observed that overexpression of Bcl-2 leads to autonomous calcium oscillations in cells. Upon further investigation, we discovered that Bcl-2, by upregulating cell membrane calcium channels such as PMCA, NCX1, ORAI1, STIM1, induces calcium oscillations to regulate intracellular calcium levels and prevent cell apoptosis. This is particularly evident in the case of PMCA and NCX1, as they are channel proteins responsible for transporting calcium directly out of the cell. To demonstrate the association between Bcl-2-induced calcium oscillations and PMCA as well as NCX1, we conducted studies using inhibitors for both, namely RES and ORM-10103. The results showed that under treatment with inhibitors, the calcium oscillations triggered by Bcl-2 were significantly reduced or even disappeared, especially in PMCA, showing that PMCA and NCX1 indeed play an important role in the mechanism of Bcl-2 avoiding apoptosis. This is a strikingly different finding from previous studies. However, the mechanism by which Bcl-2 influences calcium channels such as PMCA and NCX1 may be a topic that requires further investigation in the future. In conclusion, our research suggests that Bcl-2 prevents cell death by modulating the transport of calcium ions across the cell membrane, leading to the formation of calcium oscillations. This provides new directions for future studies.

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