Roles of PTEN-induced putative kinase 1 and dynamin-related protein 1 in transient global ischemia-induced hippocampal neuronal injury

Shang Der Chen, Tsu Kung Lin, Ding I. Yang, Su Ying Lee, Fu-Zen Shaw, Chia Wei Liou, Yao Chung Chuang

Research output: Contribution to journalArticle

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Abstract

Recent studies showed that increased mitochondrial fission is an early event of cell death during cerebral ischemia and dynamin-related protein 1 (Drp1) plays an important role in mitochondrial fission, which may be regulated by PTEN-induced putative kinase 1 (PINK1), a mitochondrial serine/threonine-protein kinase thought to protect cells from stress-induced mitochondrial dysfunction and regulate mitochondrial fission. However, the roles of PINK1 and Drp1 in hippocampal injury caused by transient global ischemia (TGI) remain unknown. We therefore tested the hypothesis that TGI may induce PINK1 causing downregulation of Drp1 phosphorylation to enhance hippocampal neuronal survival, thus functioning as an endogenous neuroprotective mechanism. We found progressively increased PINK1 expression in the hippocampal CA1 subfield1-48 h following TGI, reaching the maximal level at 4 h. Despite lack of changes in the expression level of total Drp1 and phosphor-Drp1 at Ser637, TGI induced a time-dependent increase of Drp1 phosphorlation at Ser616 that peaked after 24 h. Notably, PINK1-siRNA increased p-Drp1(Ser616) protein level in hippocampal CA1 subfield 24 h after TGI. The PINK1 siRNA also aggravated the TGI-induced oxidative DNA damage with an increased 8-hydroxy-deoxyguanosine (8-OHdG) content in hippocampal CA1 subfield. Furthermore, PINK1 siRNA also augmented TGI-induced apoptosis as evidenced by the increased numbers of TUNEL-positive staining and enhanced DNA fragmentation. These findings indicated that PINK1 is an endogenous protective mediator vital for neuronal survival under ischemic insult through regulating Drp1 phosphorylation at Ser616.

Original languageEnglish
Pages (from-to)397-403
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume460
Issue number2
DOIs
Publication statusPublished - 2015 May 1

Fingerprint

Dynamin I
Dynamins
Ischemia
Wounds and Injuries
Mitochondrial Dynamics
Proteins
Small Interfering RNA
Phosphorylation
PTEN-induced putative kinase
Deoxyguanosine
Protein-Serine-Threonine Kinases
DNA
In Situ Nick-End Labeling
DNA Fragmentation
Cell death
Brain Ischemia
Phosphors
DNA Damage
Cell Death
Down-Regulation

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Chen, Shang Der ; Lin, Tsu Kung ; Yang, Ding I. ; Lee, Su Ying ; Shaw, Fu-Zen ; Liou, Chia Wei ; Chuang, Yao Chung. / Roles of PTEN-induced putative kinase 1 and dynamin-related protein 1 in transient global ischemia-induced hippocampal neuronal injury. In: Biochemical and Biophysical Research Communications. 2015 ; Vol. 460, No. 2. pp. 397-403.
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Roles of PTEN-induced putative kinase 1 and dynamin-related protein 1 in transient global ischemia-induced hippocampal neuronal injury. / Chen, Shang Der; Lin, Tsu Kung; Yang, Ding I.; Lee, Su Ying; Shaw, Fu-Zen; Liou, Chia Wei; Chuang, Yao Chung.

In: Biochemical and Biophysical Research Communications, Vol. 460, No. 2, 01.05.2015, p. 397-403.

Research output: Contribution to journalArticle

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AU - Shaw, Fu-Zen

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