SREBP versus NRF1 Behavior Based on Cholesterol Sensing in Niemann-Pick Type C Using a COS-7 Model

Authors

Christine Tran, Belmont UniversityFollow
Jacob McIntyre, Belmont UniversityFollow
Felicity Sterling PhD, Belmont UniversityFollow

Publication Date

Fall 11-2024

College

Sciences and Mathematics, College of

Department

Biology, Department of

SURS Faculty Advisor

Felicity Sterling

Presentation Type

Poster Presentation

Abstract

Niemann-Pick disease type C (NPC) is a rare genetic disorder where cholesterol and lipid transport are blocked leading to accumulation in the lysosomes (National Organization of Rare Diseases (NORD), 2024; Boston Children’s Hospital). This accumulation can lead to neurological issues, such as developmental delay, ataxia, seizures, and early onset of dementia (Patterson, 2000). To study this disease more in depth, scientists have identified a drug called U18666A that induces NPC in the cells it is administered to (Lu, et al., 2015) which allows for the study of other structures and biomolecules in the sterol sensing and transport pathways.

Cholesterol has different uses throughout the cell. In the endoplasmic reticulum (ER), cholesterol is used for maintenance of mobility in ER proteins and protein secretion (Rigsdale, et al., 2006). When the cholesterol is transported to the ER from the lysosome, it is sensed by both the SREBP complex and NRF1. Although SREBP has been well studied in its pathway for de novo cholesterol synthesis (Horton, et al., 2002), less is known about NRF1 activity in NPC. This leads to the inquiry of how NRF1 reacts and its downstream effects in comparison to the SREBP complex. NPC was induced in COS-7 cells using the U18666A drug and imaged through immunofluorescence staining in order to look into these effects. As studied previously, SREBP was found to stay in the ER when cholesterol was detected and left the ER when NPC was induced. NRF1 reacted similarly when cholesterol was detected in the ER; however, it was also found to both stay in the ER and travel to the nucleus when NPC was induced.

Recommended Citation

Tran, Christine; McIntyre, Jacob; and Sterling, Felicity PhD, "SREBP versus NRF1 Behavior Based on Cholesterol Sensing in Niemann-Pick Type C Using a COS-7 Model" (2024). Science University Research Symposium (SURS). 212.
https://repository.belmont.edu/surs/212