Inhibition of the human secretory pathway Ca 2+ , Mn 2+ -ATPase1a by 1,3-thiazole derivatives

The human Golgi/secretory pathway Ca ,Mn -ATPase 1 (hSPCA1) transports Ca and Mn into the Golgi lumen. Studies of the biological functions of hSPCA1 are limited by a lack of selective pharmacological tools for SPCA1 inhibition. The aim of this study was therefore to identify compounds that specifica...

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Bibliographic Details
Published inBiochemical and biophysical research communications Vol. 614; p. 56
Main Authors Yamamoto-Hijikata, Sachiko, Suga, Kei, Homareda, Haruo, Ushimaru, Makoto
Format Journal Article
LanguageEnglish
Published United States 06.05.2022
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Summary:The human Golgi/secretory pathway Ca ,Mn -ATPase 1 (hSPCA1) transports Ca and Mn into the Golgi lumen. Studies of the biological functions of hSPCA1 are limited by a lack of selective pharmacological tools for SPCA1 inhibition. The aim of this study was therefore to identify compounds that specifically inhibit hSPCA1 activity. We found that five 1,3-thiazole derivatives exhibited inhibitory action towards the ATP hydrolysis activity of hSPCA1a in a concentration-dependent manner. Among the derivatives tested, compound 1 was the most potent, completely inhibiting hSPCA1a activity with a half-maximal inhibition (IC ) value of 0.8 μM. Compound 1 also partially inhibited the activity of another Ca ,Mn -ATPase (hSPCA2) and Ca -ATPase (rSERCA1a), but had no effect on Na ,K -ATPase or H ,K -ATPase. Treatment of HeLa cells with compound 1 led to fragmentation of the Golgi ribbon into smaller stacks. In addition, compound 1 mobilized intracellular Ca in HeLa cells that had been pre-treated with thapsigargin. Therefore, based on its selectivity and potency, compound 1 may be a valuable tool with which to further explore the role of SPCA1 in cellular processes.
ISSN:1090-2104