Anya Parikh
Research Mentor: Ruma Banerjee
Mentor Department: Biological Chemistry, Medicine
Author(s): Anya Parikh, Jutta Diessl, Ruma Banerjee
Session: Session 5 (2:00 PM – 2:50 PM)
Presentation Type: Poster 34
Abstract
Hydrogen sulfide (H2S) is a signaling molecule found in colonocytes that regulates physiological processes at low concentrations and inhibits complex IV in the mitochondrial electron transport chain (ETC) at high concentrations. Inhibition of the ETC leads to a reductive shift that is marked by the overreduction of the coenzyme Q (CoQ) pool. Preliminary data in the Banerjee laboratory shows that H2S induces an increase in intracellular copper (Cu) across human cell lines. In the current working model, Cu is imported via zinc transporter 1 (Znt1) and forms a complex with a low molecular weight ligand e.g. carbamoyl-aspartate, which builds up in response to a sulfide-induced reductive shift. Following removal of the sulfide stress and re-exposure to normal air, Cu returns to baseline levels. We are examining the time course of Cu loss. Further, we are using Lactobacillus brevis NADH oxidase (LbNOX), an NADH oxidase that raises the NAD+/NADH ratio in cells, to assess whether it attenuates sulfide-induced Cu accumulation. Lastly, we are evaluating the role of Znt1 as a potential Cu importer in sulfide-treated cells. For this, Cu quantification via inductively coupled plasma mass spectrometry (ICP-MS) was performed in wild type, LbNOX expressing, and Znt1 knockdown HT-29 colon adenocarcinoma cells with or without sulfide exposure. After 8 hours of re-exposure to normal air, Cu levels returned to near basal levels in sulfide-treated cells. The expression of LbNOX did not prevent the buildup of Cu in sulfide-treated cells. However, Znt1 knockout cells attenuated sulfide-induced Cu accumulation compared to the control cell line.
