PMID- 34171402
OWN - NLM
STAT- MEDLINE
DCOM- 20220322
LR  - 20220322
IS  - 1873-2747 (Electronic)
IS  - 0361-9230 (Linking)
VI  - 174
DP  - 2021 Sep
TI  - N2L, a novel lipoic acid-niacin dimer, attenuates ferroptosis and decreases lipid 
      peroxidation in HT22 cells.
PG  - 250-259
LID - S0361-9230(21)00188-X [pii]
LID - 10.1016/j.brainresbull.2021.06.014 [doi]
AB  - Ferroptosis, a new type of programmed cell death discovered in recent years, 
      plays an important role in many neurodegenerative diseases. N2L is a novel lipoic 
      acid-niacin dimer regulating lipid metabolism with multifunction, including 
      antioxidant effect. It also exerts neuroprotective effects against glutamate- or 
      beta-amyloid (Abeta) -induced cell death. Because reactive oxygen species (ROS) play an 
      essential role in ferroptosis, we hypothesize that N2L might protect cells from 
      ferroptosis. Here, we investigated the protective effect of N2L and the 
      underlying mechanism(s) under RAS-selective lethality 3 (RSL3) treatment in HT22 
      cells. RSL3 decreased the cell viability and induced excessive accumulation of 
      ROS in HT22 cells. N2L pretreatment effectively protected HT22 cells against 
      lipid peroxidation. What's more, N2L recovered glutathione peroxidase 4 (GPX4) 
      expression and blocked the increase of Cyclooxygenase-2 (cox-2) and acyl-CoA 
      synthetase long-chain family member 4 (ACSL4) protein expressions. Moreover, N2L 
      also significantly prevented Ferritin Heavy Chain 1 (FTH1) from downregulation 
      and maintained iron homeostasis. Finally, N2L pretreatment could decrease c-Jun 
      N-terminal kinase (JNK) / extracellular regulated protein kinases (ERK) 
      activation induced by RSL3. Taken together, our results showed that N2L could 
      protect HT22 cells from RSL3-induced ferroptosis through decreasing lipid 
      peroxidation and JNK/ERK activation. And N2L could be a ferroptosis inhibitor for 
      the therapy of ferroptosis-related diseases, such as Alzheimer's disease.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Peng, Weijia
AU  - Peng W
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR 
      China.
FAU - Zhu, Zeyu
AU  - Zhu Z
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR 
      China.
FAU - Yang, Yang
AU  - Yang Y
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR 
      China.
FAU - Hou, Jiawei
AU  - Hou J
AD  - School of Medicine, Sun Yat-sen University, Guangzhou, 510006, PR China.
FAU - Lu, Junfeng
AU  - Lu J
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR 
      China.
FAU - Chen, Chen
AU  - Chen C
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, PR 
      China.
FAU - Liu, Fang
AU  - Liu F
AD  - School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, 
      Guangzhou, 510006, PR China.
FAU - Pi, Rongbiao
AU  - Pi R
AD  - School of Medicine, Sun Yat-sen University, Guangzhou, 510006, PR China. 
      Electronic address: pirb@mail.sysu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210624
PL  - United States
TA  - Brain Res Bull
JT  - Brain research bulletin
JID - 7605818
RN  - 0 (Antioxidants)
RN  - 0 (Hypolipidemic Agents)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Reactive Oxygen Species)
RN  - 2679MF687A (Niacin)
RN  - 73Y7P0K73Y (Thioctic Acid)
RN  - E1UOL152H7 (Iron)
SB  - IM
MH  - Animals
MH  - Antioxidants/*pharmacology
MH  - Cell Line
MH  - Ferroptosis/*drug effects
MH  - Hypolipidemic Agents/*pharmacology
MH  - Iron/metabolism
MH  - Lipid Peroxidation/*drug effects
MH  - MAP Kinase Signaling System/drug effects
MH  - Mice
MH  - Neuroprotective Agents/*pharmacology
MH  - Niacin/*pharmacology
MH  - Reactive Oxygen Species/metabolism
MH  - Thioctic Acid/*pharmacology
OTO - NOTNLM
OT  - Extracellular regulated protein kinase
OT  - Ferroptosis
OT  - Lipid peroxidation
OT  - N2L
OT  - c-Jun N-terminal kinase
EDAT- 2021/06/26 06:00
MHDA- 2022/03/23 06:00
CRDT- 2021/06/25 20:12
PHST- 2021/04/05 00:00 [received]
PHST- 2021/06/15 00:00 [revised]
PHST- 2021/06/18 00:00 [accepted]
PHST- 2021/06/26 06:00 [pubmed]
PHST- 2022/03/23 06:00 [medline]
PHST- 2021/06/25 20:12 [entrez]
AID - S0361-9230(21)00188-X [pii]
AID - 10.1016/j.brainresbull.2021.06.014 [doi]
PST - ppublish
SO  - Brain Res Bull. 2021 Sep;174:250-259. doi: 10.1016/j.brainresbull.2021.06.014. 
      Epub 2021 Jun 24.