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. 2021 Mar 25;13(7):1518. doi: 10.3390/cancers13071518

Figure 3.

Figure 3

Induction of tricarboxylic acid (TCA) cycle through pyruvate and dissociated calcium under hypoxia. Dephosphorylation and activation of pyruvate dehydrogenase (PDH) were stimulated by calcium., and pyruvate was utilized for TCA cycle restoration, leading to an increase in a-ketoglutarate (α-KG). (A) Schematic illustration of TCA cycle restoration by pyruvate and dissociated calcium. PDH activity is inhibited by kinase activity of pyruvate dehydrogenase kinase (PDK) under hypoxia [18], and the inactivation of PDH can be confirmed by an increase in phospho-PDH (pPDH) [19]. However, the increase of intracellular calcium upregulates phosphatase activity followed by PDH activation. Then, the TCA cycle is coupled, and the converted pyruvate is utilized in the metabolic process of the active TCA cycle. (B) Decreased phospho-PDH (pPDH) at the protein level following 2.5 mM CaLac treatment in CRC cells. Uncropped blots were indicated in Figure S5 (C,D) Quantitative analysis of pPDH expression in CRC cells using FITC-tagged pPDH. ** p < 0.001 vs. Untreated. Results are presented as mean ± standard deviation.