Nicotinamide Adenine Dinucleotide Protects against Spinal Cord Ischemia Reperfusion Injury-Induced Apoptosis by Blocking Autophagy.

Abstract

The role of autophagy, neuroprotective mechanisms of nicotinamide adenine dinucleotide (NAD+), and their relationship in spinal cord ischemic reperfusion injury (SCIR) was assessed. Forty-eight Sprague-Dawley rats were divided into four groups: sham, ischemia reperfusion (I/R), 10 mg/kg NAD+, and 75 mg/kg NAD+. Western blotting, immunofluorescence, and immunohistochemistry were used to assess autophagy and apoptosis. Basso, Beattie, and Bresnahan (BBB) scores were used to assess neurological function. Expression levels of Beclin-1, Atg12-Atg5, LC3B-II, cleaved caspase 3, and Bax were upregulated in the I/R group and downregulated in the 75 mg/kg NAD+ group; p-mTOR, p-AKT, p62, and Bcl-2 were downregulated in the I/R group and upregulated in the 75 mg/kg NAD+ group. Numbers of LC3B-positive, caspase 3-positive, Bax-positive, and TUNEL-positive cells were significantly increased in the I/R group and decreased in the 75 mg/kg NAD+ group. The mean integrated option density of Bax increased and that of Nissl decreased in the I/R group, and it decreased and increased, respectively, in the 75 mg/kg NAD+ group. BBB scores significantly increased in the 75 mg/kg NAD+ group relative to the I/R group. No difference was observed between I/R and 10 mg/kg NAD+ groups for these indicators. Therefore, excessive and sustained autophagy aggravates SCIR; administration of NAD+ alleviates injury.

• Authors: Lei Xie, Sifei Yu, Zhenfei Wang, Kai Yang, Zhuochao Liu, Changwei Li, Yu Liang
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2017 Pg. 7063874 ( 2017) ISSN: 1942-0994 [Electronic] United States
• PMID: 28367271 (Publication Type: Journal Article)

Chemical References

• Beclin-1
• Neuroprotective Agents
• bcl-2-Associated X Protein
• NAD
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases
• Caspase 3

Topics

• Animals
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Beclin-1 (metabolism)
• Caspase 3 (metabolism)
• Down-Regulation (drug effects)
• Immunohistochemistry
• Male
• Microscopy, Fluorescence
• NAD (pharmacology, therapeutic use)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (drug therapy)
• Spinal Cord Ischemia (pathology)
• TOR Serine-Threonine Kinases (metabolism)
• Up-Regulation (drug effects)
• bcl-2-Associated X Protein (metabolism)