期刊
JOURNAL OF PROTEOME RESEARCH
卷 21, 期 2, 页码 301-312出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.1c00187
关键词
HIV-1; cathepsin B; SAPC; HAND; apoptosis; TMT
资金
- National Institutes of Health National Institute of General Medical Sciences (NIGMS) [SC1GM11369-01]
- National Institute on Minority Health and Health Disparities [U54MD007600]
- National Institute of General Medical Sciences of the National Institutes of Health [P20GM103475]
- Comprehensive Cancer Center of the UPR
This study investigated the deregulated proteins in neurons exposed to HIV-infected macrophage-conditioned media after inhibiting cathepsin B (CATB) or serum amyloid P component (SAPC) using tandem mass tag proteomics labeling. The results suggest that CATB, SAPC, and apoptosis-related proteins could be potential targets against HIV-induced neuronal degeneration.
Human immunodeficiency virus 1 (HIV-1) infects blood monocytes that cross the blood-brain barrier to the central nervous system, inducing neuronal damage. This is prompted by the secretion of viral and neurotoxic factors by HIV-infected macrophages, resulting in HIV-associated neurocognitive disorders. One of these neurotoxic factors is cathepsin B (CATB), a lysosomal cysteine protease that plays an important role in neurodegeneration. CATB interacts with the serum amyloid P component (SAPC), contributing to HIV-induced neurotoxicity. However, the neuronal apoptosis pathways triggered by CATB and the SAPC remain unknown. We aimed to elucidate these pathways in neurons exposed to HIV-infected macrophage-conditioned media before and after the inhibition of CATB or the SAPC with antibodies using tandem mass tag proteomics labeling. Based on the significant fold change (FC) >= vertical bar 2 vertical bar and p-value < 0.05 criteria, a total of 10, 48, and 13 proteins were deregulated after inhibiting CATB, SAPC antibodies, and the CATB inhibitor CA-074, respectively. We found that neurons exposed to the CATB antibody and SAPC antibody modulate similar proteins (TUBA1A and CYPA/PPIA) and unique proteins (LMNA and HSPH1 for the CATB antibody) or (CFL1 and PFN1 for the SAPC antibody). CATB, SAPC, or apoptosis-related proteins could become potential targets against HIV-induced neuronal degeneration.
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