MARCH1 Inhibits the Inflammation and Cell Proliferation via Enhancing NLRP5 Ubiquitination in a Subarachnoid Hemorrhage Cells Model

Ai Yan, Jufang He, Yuntao Li, Xiaohu Nie, Bin Lu

Article ID: 7485
Vol 37, Issue 8, 2023
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20233708.429
Received: 8 September 2023; Accepted: 8 September 2023; Available online: 8 September 2023; Issue release: 8 September 2023

Abstract

Background: Subarachnoid hemorrhage (SAH) is a cerebrovascular illness with high mortality. Inflammation is considered as a potential pathogenic factor of SAH occurrence. Membrane-associated ring-CH type finger 1 (MARCH1) has been implicated to inhibit immune response based on ubiquitination activity, indicating the potential treatment for SAH. However, the role of MARCH1 in SAH remains unclear. We aimed to explore the role of MARCH1 in SAH. Methods: Enzyme-linked immunosorbent assay (ELISA) was performed to measure the levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in SAH patients and healthy donors. Oxyhemoglobin (OxyHb) was applied to PC12 cells to establish the SAH cell model. After OxyHb treatment, cell proliferation in PC12 cells was assessed using the cell counting kit-8 (CCK-8) kit. Lentiviruses were used to knock down or overexpress MARCH1 expression. Real-time PCR and western blot assays were used to detect the mRNA and protein expression levels of MARCH1. Results: The levels of IL-1β and IL-18 were significantly higher in SAH patients compared to healthy donors (p < 0.001), with a notable upregulation observed in the advanced stages of SAH (p < 0.05 and p < 0.001). OxyHb enhanced IL-18 and IL-1β (p < 0.001) but decreased MARCH1 expression (p < 0.001) in a time-dependent manner in PC12 cells (p < 0.001). Besides, MARCH1 could inhibit SAH-induced inflammation and promote the proliferation of cells (p < 0.001). MARCH1 decreased the protein levels of NACHT (central nucleotide-binding and oligomerization), leucine-rich repeat (LRR), and Pyrin domain (PYD) containing proteins 5 (NLRP5) (p < 0.001) by promoting its ubiquitination. Furthermore, these effects could be reversed by the overexpression of NLRP5 in the SAH cell model (p < 0.001). Conclusions: Our study revealed that MARCH1 could inhibit the inflammation and promote cell proliferation in the SAH cell model by enhancing NLRP5 ubiquitination. MARCH1 and NLRP5 could be potential targets for the treatment of SAH. However, the in vivo experiment is needed to further verify this conclusion.


Keywords

subarachnoid hemorrhage;MARCH1;NLRP5;ubiquitination;inflammation


References

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