Лизофоспатидилхолин вызывает церамид синтаза-2 в первичной культурной модели астроцитопатии: потенциальная терапевтическая цель при множественном склерозе.
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Mohapatra Abhipsa, Amarjeet, Pancholi Bhaskaranand, Babu Raja, Abate Selamu Kebamo, Garabadu Debapriya
Аннотация
Оригинал публикации
Lysophosphatidylcholine induces ceramide synthase-2 expression in primary culture model of astrocytopathy: potential therapeutic target in multiple sclerosis.
BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune condition that damages the myelin sheath of neurons in the central nervous system, resulting in compromised nerve transmission and motor impairment. The astrocytopathy is considered one of the prominent etiological factor in the pathophysiology of demyelination in MS. The expression level of ceramide synthase-2 (CS-2) is yet to be established in the pathophysiology of astrocytopathy although the derailed ceramide biosynthetic pathways is well demonstrated in the pathophysiology of demyelination. Therefore, in the present study, the expression level of CS-2 has been evaluated in lysophosphatidylcholine (LPC)-challenged primary astrocytes in the presence of anti-demyelinating agents such as Fingolimod, a clinically approved anti-demyelinating drug, and Ursolic Acid (UA), an experimentally accepted anti-demyelinating agent, in MS.
METHODS AND RESULTS: LPC (150 µg/ml) caused astrocytopathy evident by decrease in percentage of viable astrocytes, increase in percentage of apoptotic astrocytes, increase in the level of reactive oxygen species (ROS), and increase in the level of activated astrocytes. Interestingly, LPC significantly increased the expression level of CS-2 in the primary culture of astrocytes where as fingolimod and UA (1, 10, and 100 µM) were able to attenuate the extent of LPC-induced astrocytopathy in the primary culture model of MS. Further, both the drugs drastically reduced the LPC-induced increase in the level of expression of CS-2 in the astrocytes.
CONCLUSIONS: These observations indicate the fact that CS-2 could be a potential target in the management of astrocytopathy and astrocytopathy-related neurological disorders including MS. In conclusion, CS-2-targeted drugs could be potential therapeutic options in the management of MS.