Understanding How Stanniocalcin-1 (STC1) Affects Apolipoprotein-1 (APOL1) Mediated Cellular Cytotoxicity
Yuliya Severynenko1, Jyoti Pant1, Jayne Raper1,2
1 Department of Biological Sciences, Hunter College, City University of New York, New York, USA.
2 The Graduate Center of the City University of New York, New York, New York, USA.
Apolipoprotein L-1 (APOL1) is an innate immunity ion-channel forming protein that provides protection against African trypanosomes. Due to a molecular arms race, people of African lineage evolved with two APOL1 variants, namely G1 and G2. These variants, also called renal risk variants, confer a higher risk of chronic kidney diseases in homozygous individuals through increased intracellular APOL1 expression in podocytes and endothelial cells. APOL1 renal risk variants are also associated with some cancers. This is apparent in the African American demographic, which already faces disproportionate health burdens. Stanniocalcin-1 (STC1) is a glycoprotein hormone, which has been shown to be significantly upregulated in kidney biopsies of patients with G1 and G2 APOL1 compared to G0 genotype APOL1. To understand the function of STC1 in APOL1 renal risk variant cytotoxicity, we overexpressed STC1 in HEK-293 derived cells with inducible APOL1 and measured Lactate dehydrogenase (LDH) in the culture medium. Cells overexpressing STC1 with no APOL1 induction were used as control. We found significantly lower LDH release in cells expressing STC1 and APOL1 compared to the control group at 24, but not 42 hours post APOL1 induction.
Our results suggest that STC1 has a protective effect on G2 mediated cytotoxicity. In the future, we plan to further investigate how STC1 reduces APOL1 mediated cellular cytotoxicity.
