Carnitine palmitoyltransferase 1C reverses cellular senescence of MRC-5 fibroblasts via regulating lipid accumulation and mitochondrial function.
Adenosine Triphosphate
/ genetics
Carnitine O-Palmitoyltransferase
/ genetics
Cell Line
Cell Proliferation
/ genetics
Cellular Senescence
/ genetics
Down-Regulation
/ genetics
Fibroblasts
/ physiology
Humans
Lipid Metabolism
/ genetics
Membrane Potential, Mitochondrial
/ genetics
Mitochondria
/ genetics
RNA, Messenger
/ genetics
Up-Regulation
/ genetics
beta-Galactosidase
/ genetics
MRC-5 fibroblasts
carnitine palmitoyltransferase 1C (CPT1C)
cellular senescence
lipidomics
mitochondrial function
Journal
Journal of cellular physiology
ISSN: 1097-4652
Titre abrégé: J Cell Physiol
Pays: United States
ID NLM: 0050222
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
19
04
2020
accepted:
16
06
2020
pubmed:
8
7
2020
medline:
9
9
2021
entrez:
8
7
2020
Statut:
ppublish
Résumé
Cellular senescence, a state of growth arrest, is involved in various age-related diseases. We previously found that carnitine palmitoyltransferase 1C (CPT1C) is a key regulator of cancer cell proliferation and senescence, but it is unclear whether CPT1C plays a similar role in normal cells. Therefore, this study aimed to investigate the role of CPT1C in cellular proliferation and senescence of human embryonic lung MRC-5 fibroblasts and the involved mechanisms. The results showed that CPT1C could reverse the cellular senescence of MRC-5 fibroblasts, as evidenced by reduced senescence-associated β-galactosidase activity, downregulated messenger RNA (mRNA) expression of senescence-associated secretory phenotype factors, and enhanced bromodeoxyuridine incorporation. Lipidomics analysis further revealed that CPT1C gain-of-function reduced lipid accumulation and reversed abnormal metabolic reprogramming of lipids in late MRC-5 cells. Oil Red O staining and Nile red fluorescence also indicated significant reduction of lipid accumulation after CPT1C gain-of-function. Consequently, CPT1C gain-of-function significantly reversed mitochondrial dysfunction, as evaluated by increased adenosine triphosphate synthesis and mitochondrial transmembrane potential, decreased radical oxygen species, upregulated respiratory capacity and mRNA expression of genes related to mitochondrial function. In summary, CPT1C plays a vital role in MRC-5 cellular proliferation and can reverse MRC-5 cellular senescence through the regulation of lipid metabolism and mitochondrial function, which supports the role of CPT1C as a novel target for intervention into cellular proliferation and senescence and suggests CPT1C as a new strategy for antiaging.
Substances chimiques
RNA, Messenger
0
Adenosine Triphosphate
8L70Q75FXE
CPT1B protein, human
EC 2.3.1.21
Carnitine O-Palmitoyltransferase
EC 2.3.1.21
beta-Galactosidase
EC 3.2.1.23
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
958-970Informations de copyright
© 2020 Wiley Periodicals LLC.
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