Proteomics

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Proteomic analysis of human macrophages overexpressing angiotensin-converting enzyme


ABSTRACT: Angiotensin converting enzyme (ACE) exerts strong modulation of myeloid cell function independently of its cardiovascular arm. The success of the ACE-overexpressing murine macrophage model, ACE 10/10, in treating microbial infections and cancer opens a new venture into whether ACE overexpression in human macrophages share these benefits. Additionally, as ACE inhibitors are a widely used antihypertensive medication, their impact on ACE expressing immune cells is of interest and currently understudied. In the present study, we utilized mass spectrometry to characterize and assess global proteomic changes in an ACE overexpressing human THP-1 cell line. Additional proteomic and cellular uptake data following treatment with an ACE C-domain selective inhibitor, lisinopril-tryptophan, was also obtained. ACE activity was significantly decreased with inhibitor treatment despite limited uptake within the cell and both RNA processing and immune pathways were significantly dysregulated with treatment. Also present were up-regulated energy and TCA cycle, cytokine and interleukin signaling proteins with ACE overexpression. A novel immune pathway that appeared both with ACE overexpression and inhibitor treatment was neutrophil degranulation. ACE overexpression within human macrophages shows similarities with ACE 10/10 murine macrophages paving the way for mechanistic studies into understanding the altered immune function.

INSTRUMENT(S): TripleTOF 6600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood, Macrophage

SUBMITTER: Tariq Ganief  

LAB HEAD: Edward Sturrock

PROVIDER: PXD052292 | Pride | 2025-06-09

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
20230908_TAG_Delia_1.wiff Wiff
20230908_TAG_Delia_1.wiff.scan Wiff
20230908_TAG_Delia_10.wiff Wiff
20230908_TAG_Delia_10.wiff.scan Wiff
20230908_TAG_Delia_11.wiff Wiff
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Publications

Proteomic Analysis of Human Macrophages Overexpressing Angiotensin-Converting Enzyme.

Oosthuizen Delia D   Ganief Tariq A TA   Bernstein Kenneth E KE   Sturrock Edward D ED  

International journal of molecular sciences 20240627 13


Angiotensin converting enzyme (ACE) exerts strong modulation of myeloid cell function independently of its cardiovascular arm. The success of the ACE-overexpressing murine macrophage model, ACE 10/10, in treating microbial infections and cancer opens a new avenue into whether ACE overexpression in human macrophages shares these benefits. Additionally, as ACE inhibitors are a widely used antihypertensive medication, their impact on ACE expressing immune cells is of interest and currently understu  ...[more]

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