PMID- 36599139
OWN - NLM
STAT- MEDLINE
DCOM- 20230106
LR  - 20230403
IS  - 1728-7731 (Electronic)
IS  - 1726-4901 (Linking)
VI  - 86
IP  - 1
DP  - 2023 Jan 1
TI  - Necrostatin-1 prevents skeletal muscle ischemia reperfusion injury by regulating 
      Bok-mediated apoptosis.
PG  - 26-33
LID - 10.1097/JCMA.0000000000000806 [doi]
AB  - BACKGROUND: Receptor interacting serine/threonine kinase 1 (RIPK1) mediates 
      apoptosis by regulating the classic proapoptotic effectors Bcl-2-associated X 
      protein (Bax) and Bcl-2 homologous antagonist/killer (Bak). Although 
      Bcl-2-related ovarian killer (Bok) is structurally similar to Bak and Bax, it is 
      unclear whether it mediates apoptosis in skeletal muscle ischemia reperfusion 
      (IR) injury. We hypothesized that by regulating Bok-mediated apoptosis, 
      inhibiting RIPK1 with necrostatin-1 would reduce skeletal muscle IR injury. 
      METHODS: Rats were randomized into four groups: sham (SM), IR, IR treated with 
      necrostatin-1 (NI), or vehicle dimethyl sulfoxide (DI). For the IR group, the 
      right femoral artery was clamped for 4 hours and then reperfused for 4 hours, and 
      for the NI and DI groups, necrostatin-1 (1.65 mg/kg) and the equal volume of 
      dimethyl sulfoxide were intraperitoneally administered prior to IR induction. The 
      structural damage of muscle tissue and protein expression of Bok, Bcl-2, and 
      cleaved caspase-3 were investigated, and apoptotic cells were identified with 
      terminal dUTP nick-end labeling (TUNEL) staining. In vitro, human skeletal muscle 
      cells (HSMCs) were exposed to 6 hours of oxygen-glucose deprivation followed by 
      normoxia for 6 hours to establish an oxygen-glucose deprivation/reoxygenation 
      (OGD/R) model. To determine the role of Bok, cell viability, lactate 
      dehydrogenase (LDH) release, and flow cytometry were examined to demonstrate the 
      effects of necrostatin-1 and Bok knockdown on the OGD/R insult of HSMCs. RESULTS: 
      Necrostatin-1 pretreatment markedly reduced IR-induced muscle damage and RIPK1, 
      Bok, and cleaved caspase-3 expression, whereas upregualted Bcl-2 expression (p < 
      0.05). Furthermore, necrostatin-1 prevented mitochondrial damage and decreased 
      TUNEL-positive muscle cells (p < 0.05). In vitro, HSMCs treated with 
      necrostatin-1 showed reduced Bok expression, increased cell viability, and 
      reduced LDH release in response to OGD/R (p < 0.05), and Bok knockdown 
      significantly blunted the OGD/R insult in HSMCs. CONCLUSION: Necrostatin-1 
      prevents skeletal muscle from IR injury by regulating Bok-mediated apoptosis.
CI  - Copyright (c) 2022, the Chinese Medical Association.
FAU - Cao, Yu
AU  - Cao Y
AD  - Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical 
      University, Zhejiang, China.
FAU - Wang, Hong-Bo
AU  - Wang HB
AD  - Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical 
      University, Zhejiang, China.
FAU - Ni, Chun-Jue
AU  - Ni CJ
AD  - Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical 
      University, Zhejiang, China.
FAU - Chen, Shun-Li
AU  - Chen SL
AD  - Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical 
      University, Zhejiang, China.
FAU - Wang, Wan-Tie
AU  - Wang WT
AD  - Institute of Ischemia-Reperfusion Injury, Wenzhou Medical University, Zhejiang, 
      China.
FAU - Wang, Liang-Rong
AU  - Wang LR
AD  - Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical 
      University, Zhejiang, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230102
PL  - Netherlands
TA  - J Chin Med Assoc
JT  - Journal of the Chinese Medical Association : JCMA
JID - 101174817
RN  - 0 (bcl-2-Associated X Protein)
RN  - EC 3.4.22.- (Caspase 3)
RN  - 0 (necrostatin-1)
RN  - YOW8V9698H (Dimethyl Sulfoxide)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - S88TT14065 (Oxygen)
RN  - IY9XDZ35W2 (Glucose)
RN  - 0 (BOK protein, human)
SB  - IM
MH  - Rats
MH  - Humans
MH  - Animals
MH  - bcl-2-Associated X Protein
MH  - Caspase 3/metabolism/pharmacology
MH  - *Dimethyl Sulfoxide/pharmacology
MH  - Apoptosis
MH  - Proto-Oncogene Proteins c-bcl-2
MH  - *Reperfusion Injury/prevention & control
MH  - Oxygen
MH  - Muscle, Skeletal/metabolism
MH  - Glucose
COIS- Conflicts of interest: The authors declare that they have no conflicts of 
      interest related to the subject matter or materials discussed in this article.
EDAT- 2023/01/05 06:00
MHDA- 2023/01/07 06:00
CRDT- 2023/01/04 16:53
PHST- 2023/01/04 16:53 [entrez]
PHST- 2023/01/05 06:00 [pubmed]
PHST- 2023/01/07 06:00 [medline]
AID - 02118582-202301000-00007 [pii]
AID - 10.1097/JCMA.0000000000000806 [doi]
PST - ppublish
SO  - J Chin Med Assoc. 2023 Jan 1;86(1):26-33. doi: 10.1097/JCMA.0000000000000806. 
      Epub 2023 Jan 2.