PMID- 37560474
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230811
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 14
DP  - 2023
TI  - L-cystathionine protects against oxidative stress and DNA damage induced by 
      oxidized low-density lipoprotein in THP-1-derived macrophages.
PG  - 1161542
LID - 10.3389/fphar.2023.1161542 [doi]
LID - 1161542
AB  - Introduction: Oxidative stress in monocyte-derived macrophages is a significant 
      pathophysiological process in atherosclerosis. L-cystathionine (L-Cth) acts as a 
      scavenger for oxygen free radicals. However, the impact of L-Cth on macrophage 
      oxidative stress during atherogenesis has remained unclear. This study aimed to 
      investigate whether L-Cth affects oxidative stress in THP-1-derived macrophages 
      and its subsequent effects on DNA damage and cell apoptosis. Methods: We 
      established a cellular model of oxLDL-stimulated macrophages. The content of 
      superoxide anion, H(2)O(2), NO, and H(2)S in the macrophage were in situ detected 
      by the specific fluorescence probe, respectively. The activities of SOD, GSH-Px, 
      and CAT were measured by colorimetrical assay. The protein expressions of SOD1, 
      SOD2, and iNOS were detected using western blotting. The DNA damage and apoptosis 
      in the macrophage was evaluated using an fluorescence kit. Results: The results 
      demonstrated that oxLDL significantly increased the content of superoxide anion 
      and H(2)O(2), the expression of iNOS protein, and NO production in macrophages. 
      Conversely, oxLDL decreased the activity of antioxidants GSH-Px, SOD, and CAT, 
      and downregulated the protein expressions of SOD1 and SOD2 in macrophages. 
      However, treatment with L-Cth reduced the levels of superoxide anion, H(2)O(2), 
      and NO, as well as the protein expression of iNOS induced by oxLDL. Moreover, 
      L-Cth treatment significantly enhanced GSH-Px, SOD, and CAT activity, and 
      upregulated the expressions of SOD1 and SOD2 proteins in macrophages treated with 
      oxLDL. Furthermore, both L-Cth supplementation and activation of endogenous L-Cth 
      production suppressed DNA damage and cell apoptosis in oxLDL-injured macrophages, 
      whereas inhibition of endogenous L-Cth exacerbated the deleterious effects of 
      oxLDL. Conclusion: These findings suggest that L-Cth exerts a pronounced 
      inhibitory effect on the oxidative stress, subsequent DNA damage and cell 
      apoptosis in oxLDL-stimulated THP-1 monocytes. This study deepens our 
      understanding of the pathogenesis of macrophage-related cardiovascular pathology.
CI  - Copyright (c) 2023 Peng, Zhu, Kong, Tang, Du, Huang and Jin.
FAU - Peng, Hanlin
AU  - Peng H
AD  - Department of Pediatrics, Peking University First Hospital, Beijing, China.
FAU - Zhu, Mingzhu
AU  - Zhu M
AD  - Department of Pediatrics, Peking University First Hospital, Beijing, China.
FAU - Kong, Wei
AU  - Kong W
AD  - Department of Physiology and Pathophysiology, Peking University Health Science 
      Center, Beijing, China.
FAU - Tang, Chaoshu
AU  - Tang C
AD  - Department of Physiology and Pathophysiology, Peking University Health Science 
      Center, Beijing, China.
AD  - State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, 
      Beijing, China.
FAU - Du, Junbao
AU  - Du J
AD  - Department of Pediatrics, Peking University First Hospital, Beijing, China.
AD  - State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, 
      Beijing, China.
FAU - Huang, Yaqian
AU  - Huang Y
AD  - Department of Pediatrics, Peking University First Hospital, Beijing, China.
FAU - Jin, Hongfang
AU  - Jin H
AD  - Department of Pediatrics, Peking University First Hospital, Beijing, China.
LA  - eng
PT  - Journal Article
DEP - 20230725
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC10408194
OTO - NOTNLM
OT  - DNA damage
OT  - L-cystathionine
OT  - macrophage
OT  - oxidative stress
OT  - oxidized low-density lipoprotein
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/08/10 06:43
MHDA- 2023/08/10 06:44
PMCR- 2023/07/25
CRDT- 2023/08/10 04:30
PHST- 2023/02/08 00:00 [received]
PHST- 2023/07/13 00:00 [accepted]
PHST- 2023/08/10 06:44 [medline]
PHST- 2023/08/10 06:43 [pubmed]
PHST- 2023/08/10 04:30 [entrez]
PHST- 2023/07/25 00:00 [pmc-release]
AID - 1161542 [pii]
AID - 10.3389/fphar.2023.1161542 [doi]
PST - epublish
SO  - Front Pharmacol. 2023 Jul 25;14:1161542. doi: 10.3389/fphar.2023.1161542. 
      eCollection 2023.