tiRNAs as a novel biomarker for cell damage assessment in in vitro ischemia-reperfusion model in rat neuronal PC12 cells.

Abstract

The disruption of appropriate cellular stress responses is implicated in the pathogenesis of different neurological disorders including ischemic injury. Early diagnosis and treatment are often associated with better prognosis in ischemic stroke patients. Thus, there is an urgent need to improve the speed and accuracy of stroke diagnosis by developing highly sensitive stroke biomarkers. We recently reported that transfer RNA (tRNA) was involved in cell stress response pathways. Under cell stress conditions, mature tRNA is cleaved by a specific ribonuclease, angiogenin, generating tRNA-derived stress-induced RNA (tiRNA). To study tiRNA generation in an in vitro model of ischemic-reperfusion injury, we used the rat neuronal cell line, PC12, in combination with analysis of SYBR staining and immuno-northern blotting using anti-1-methyladenosine antibody, which detects 1-methyladenosine (m1A) modification of tRNA. We demonstrated that oxygen-glucose deprivation induced tRNA cleavage and tiRNA generation. Time course analysis showed a dramatic up-regulation of tiRNA generation by oxygen-glucose deprivation (OGD) which started a few minutes after reperfusion. Minocycline, a neuroprotective antibiotic, treatment protected PC12 cells against OGD-reperfusion cell damage resulting in a marked down-regulation of the generated tiRNA. Our findings show that cleavage of tRNA and tiRNA generation in rat neuronal PC12 cells occurs with reperfusion injury and the detection of tiRNA could be used as a potential cell damage marker and treatment effect indicator for this type of injury.

• Authors: Alaa Elkordy, Sherif Rashad, Heba Shehabeldeen, Eikan Mishima, Kuniyasu Niizuma, Takaaki Abe, Teiji Tominaga
• Journal: Brain research (Brain Res) Vol. 1714 Pg. 8-17 (07 01 2019) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 30779912 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Biomarkers
• 1-methyladenosine
• RNA, Transfer
• angiogenin
• Ribonuclease, Pancreatic
• Glucose
• Adenosine
• Oxygen

Topics

• Adenosine (analogs & derivatives, metabolism)
• Animals
• Biomarkers
• Cell Survival (drug effects)
• Glucose (metabolism)
• Hypoxia (metabolism)
• Ischemia (genetics, metabolism)
• Neurons (metabolism)
• Oxygen (metabolism)
• PC12 Cells
• RNA, Transfer (genetics, metabolism)
• Rats
• Reperfusion Injury (genetics, metabolism)
• Ribonuclease, Pancreatic (metabolism)
• Stress, Physiological (genetics)
• Stroke (diagnosis)