Evidence of Post-translational Modifications of Proteins in Clinical Samples of Stroke after Decompressive Craniectomy

Author: Katta Sireesha, Dulam Vandana, K.V.V. Satyanarayana Murthy and Nakka Venkata Prasuja

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Abstract

Stroke is the leading cause of mortality and disability the world over. In India, stroke stands as the fourth leading cause of death. Currently, no treatment strategies exist for stroke except for thrombolytics. Stroke pathology is complex that activates multiple mechanisms of cell death pathways, thus requiring extensive investigation. The present study focused on the activation of post-translational modifications (PTMs) of proteins that decides the fate of neuronal death, such as protein ubiquitination, SUMOylation, and phosphorylation, in clinical samples of stroke collected from patients who underwent decompressive craniotomy or craniectomy (DC). Tissues of brain cortex were collected from patients after emergency DC with large Middle Cerebral Artery (MCA) infarcts. We used brain cortex tissue samples collected after MCA occlusion in rats to analyze protein ubiquitination. We performed histological analysis using hematoxylin and eosin and immunofluorescence staining. We report the following critical findings in clinical samples of stroke: 1. Altered morphological features of necrosis, 2. A pronounced expression of SUMO-2/3 protein confined to the nucleus, indicating a possible role in modulating gene expression, 3. Accumulation of abnormal or ubiquitinated proteins, 4. Phosphorylation of eukaryotic initiation factor 2 alpha (peIF2α) is one of the hallmarks of endoplasmic reticulum (ER) stress or unfolded protein response. The present study using clinical samples collectively indicates that PTMs are associated with stroke-induced brain damage and provide insights into understanding stroke pathophysiology and help develop newer therapeutic strategies aiming at stroke/cerebral ischemia to curtail brain damage.

Keywords

Stroke, Ubiquitin, SUMO, peIF2α, Neuroprotection

Conclusion

PTMs critically regulate the fate of neuronal cell death and survival in the post-stroke brain. Stroke leads to protein abnormality and hampers the protein quality control mechanism, which is detrimental to the survival of neurons. Our study in human stroke samples (brain cortex) provides substantial evidence and a possible role for PTMs such as ubiquitination, eIF2α Phosphorylation (a marker of ER stress or UPR), and SUMO-2/3) that play a critical role in regulating post-ischemic neuronal death. This evidence provides better insight into understanding the pathophysiology underlying stroke damage.

References

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How to cite this article

Katta Sireesha, Dulam Vandana, K.V.V. Satyanarayana Murthy and Nakka Venkata Prasuja (2023). Evidence of Post-translational Modifications of Proteins in Clinical Samples of Stroke after Decompressive Craniectomy. Biological Forum – An International Journal, 15(3): 21-26.