PMID- 22113203
OWN - NLM
STAT- MEDLINE
DCOM- 20120606
LR  - 20230815
IS  - 1554-8635 (Electronic)
IS  - 1554-8627 (Linking)
VI  - 8
IP  - 1
DP  - 2012 Jan
TI  - Induction of autophagy contributes to the neuroprotection of nicotinamide 
      phosphoribosyltransferase in cerebral ischemia.
PG  - 77-87
LID - 10.4161/auto.8.1.18274 [doi]
AB  - Recent reports indicate that autophagy serves as a stress response and may 
      participate in pathophysiology of cerebral ischemia. Nicotinamide 
      phosphoribosyltransferase (Nampt, also known as visfatin), the rate-limiting 
      enzyme in mammalian NAD (+) biosynthesis, protects against ischemic stroke 
      through inhibiting neuronal apoptosis and necrosis. This study was taken to 
      determine the involvement of autophagy in neuroprotection of Nampt in cerebral 
      ischemia. Middle cerebral artery occlusion (MCAO) in rats and oxygen-glucose 
      deprivation (OGD) in cultured cortical neurons were performed. Nampt was 
      overexpressed or knocked-down using lentivirus-mediated gene transfer in vivo and 
      in vitro. Immunochemistry (LC3-II), electron microscope and immunoblotting assays 
      (LC3-II, beclin-1, mammalian target of rapamycin [mTOR], S6K1 and tuberous 
      sclerosis complex-2 [TSC2]) were performed to assess autophagy. We found that 
      overexpression of Nampt increased autophagy (LC3 puncta immunochemistry staining, 
      LC3-II/beclin-1 expression and autophagosomes number) both in vivo and in vitro 
      at 2 hours after MCAO. At the early stage of OGD, autophagy inducer rapamycin 
      protected against neuronal injury induced by Nampt knockdown, whereas autophagy 
      inhibitor 3-methyladenine abolished the neuroprotective effect of Nampt partly. 
      Overexpression or knockdown of Nampt regulated the phosphorylation of mTOR and 
      S6K1 signaling pathway upon OGD stress through enhancing phosphorylation of TSC2 
      at Ser1387 but not Thr1462 site. Furthermore, in cultured SIRT1-knockout neurons, 
      the regulation of Nampt on autophagic proteins LC3-II and beclin-1 was abolished. 
      Our results demonstrate that Nampt promotes neuronal survival through inducing 
      autophagy via regulating TSC2-mTOR-S6K1 signaling pathway in a SIRT1-dependent 
      manner during cerebral ischemia.
FAU - Wang, Pei
AU  - Wang P
AD  - Department of Pharmacology, Second Military Medical University, Shanghai, China.
FAU - Guan, Yun-Feng
AU  - Guan YF
FAU - Du, Hui
AU  - Du H
FAU - Zhai, Qi-Wei
AU  - Zhai QW
FAU - Su, Ding-Feng
AU  - Su DF
FAU - Miao, Chao-Yu
AU  - Miao CY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120101
PL  - United States
TA  - Autophagy
JT  - Autophagy
JID - 101265188
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Tsc2 protein, mouse)
RN  - 0 (Tsc2 protein, rat)
RN  - 0 (Tuberous Sclerosis Complex 2 Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 1114-81-4 (Phosphothreonine)
RN  - 17885-08-4 (Phosphoserine)
RN  - 5142-23-4 (3-methyladenine)
RN  - EC 2.4.2.12 (Nicotinamide Phosphoribosyltransferase)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.5.1.- (Sirt1 protein, mouse)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - IY9XDZ35W2 (Glucose)
RN  - JAC85A2161 (Adenine)
RN  - S88TT14065 (Oxygen)
SB  - IM
EIN - Autophagy. 2022 Jan;18(1):233. PMID: 32013695
MH  - Adenine/analogs & derivatives/pharmacology
MH  - Animals
MH  - *Autophagy/drug effects
MH  - Brain Ischemia/complications/*enzymology/*prevention & control
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Glucose/deficiency
MH  - Infarction, Middle Cerebral Artery/enzymology/pathology
MH  - Mice
MH  - Neurons/drug effects/enzymology/pathology
MH  - Neuroprotective Agents/*metabolism
MH  - Nicotinamide Phosphoribosyltransferase/*metabolism
MH  - Oxygen
MH  - Phagosomes/ultrastructure
MH  - Phosphorylation/drug effects
MH  - Phosphoserine/metabolism
MH  - Phosphothreonine
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Ribosomal Protein S6 Kinases/metabolism
MH  - Signal Transduction/drug effects
MH  - Sirtuin 1/metabolism
MH  - Stress, Physiological/drug effects
MH  - Stroke/complications/enzymology/pathology
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Tuberous Sclerosis Complex 2 Protein
MH  - Tumor Suppressor Proteins/metabolism
EDAT- 2011/11/25 06:00
MHDA- 2012/06/07 06:00
CRDT- 2011/11/25 06:00
PHST- 2011/11/25 06:00 [entrez]
PHST- 2011/11/25 06:00 [pubmed]
PHST- 2012/06/07 06:00 [medline]
AID - 18274 [pii]
AID - 10.4161/auto.8.1.18274 [doi]
PST - ppublish
SO  - Autophagy. 2012 Jan;8(1):77-87. doi: 10.4161/auto.8.1.18274. Epub 2012 Jan 1.