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Nitrosative stress induces downregulation of ribosomal protein genes via MYCT1 in vascular smooth muscle cells.
- Source :
-
European review for medical and pharmacological sciences [Eur Rev Med Pharmacol Sci] 2021 Sep; Vol. 25 (18), pp. 5653-5663. - Publication Year :
- 2021
-
Abstract
- Objective: In our previous genomic studies in human intracranial aneurysms, we observed downregulations in the expression of a number of ribosomal protein genes and the c-Myc-related gene MYC target 1 (MYCT1). So far there is no information about the roles of MYCT1 in vascular cells. Our study aims to investigate the functional roles of MYCT1 in vascular smooth muscle cells (SMCs).<br />Materials and Methods: Primary SMCs were isolated from rat thoracic aorta and cultured in vitro. The mRNA and protein expressions were determined by real-time PCR and western blot respectively. Apoptosis was detected by measuring caspase 3/7 activity. Collagen production was determined with ELISA.<br />Results: Using PCR, we validated our previous genomic data showing that the expressions of MYCT1 and ribosomal protein genes were decreased in human aneurysm tissues. In vascular SMCs, we showed that nitrosative stress downregulated the expression of both MYCT1 and ribosomal proteins. Knockdown of MYCT1 mimicked the effects of nitrosative stress on ribosomal protein expressions, whereas overexpression of MYCT1 blunted the effects of nitrosative stress. MYCT1-dependent downregulation of ribosomal proteins compromised the protein translational capacity of the cells for collagen production. Moreover, the endogenously expressed MYCT1 in vascular SMCs was involved in maintaining normal cellular functions including survival, proliferation and migration.<br />Conclusions: MYCT1-dependent gene regulation may, at least partly, explain the downregulated expressions of ribosomal proteins observed in human intracranial aneurysms. It is suggested that MYCT1 may represent a novel molecular target for counteracting the decreased activity of aneurysmal SMCs for tissue repairmen/regeneration.
- Subjects :
- Animals
Cells, Cultured
Humans
Intracranial Aneurysm genetics
Intracranial Aneurysm physiopathology
Male
Nerve Regeneration genetics
Nerve Regeneration physiology
Nuclear Proteins metabolism
Rats, Sprague-Dawley
Rats
Down-Regulation genetics
Gene Expression genetics
Gene Expression Regulation genetics
Muscle, Smooth, Vascular metabolism
Nitrosative Stress genetics
Nitrosative Stress physiology
Nuclear Proteins genetics
Nuclear Proteins physiology
Ribosomal Proteins genetics
Ribosomal Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2284-0729
- Volume :
- 25
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- European review for medical and pharmacological sciences
- Publication Type :
- Academic Journal
- Accession number :
- 34604957
- Full Text :
- https://doi.org/10.26355/eurrev_202109_26784