Inhibition of Retinoblastoma mRNA Degradation through Poly (A) Involved in the Neuroprotective Effect of Berberine against Cerebral Ischemia

Abstract

Berberine is one kind of isoquinoline alkaloid with anti-apoptotic effects on the neurons suffering ischemia. To address the explanation for these activities, the berberine-induced cell cycle arrest during neurons suffering ischemia/reperfusion had been studied in the present study. According to the in vitro neurons with oxygen-glucose deprivation and in vivo ICR mice with cerebral ischemia/reperfusion, it was found that berberine could protect the mRNA of retinoblastoma (Rb) from degradation through its function on the poly(A) tail. The prolonged half-life of retinoblastoma 1 (gene of Rb, RB1) mRNA level secures the protein level of retinoblastoma, which facilitates cell cycle arrest of neurons in the process of ischemia/reperfusion and subsequently avoids cells entering in the apoptotic process. The poly(A) tail of RB1 mRNA, as a newly identified target of berberine, could help people focus on the interaction between berberine and mRNA to further understand the biological activities and functions of berberine.

TRPM8 in the negative regulation of TNFα expression during cold stress

“…We therefore conducted in vitro experiments to evaluate the effects of cold conditioning using PC12 cells, a neural-like cell line18.…”

“…The control group was maintained under normal conditions with normal culture medium. Cells were collected for mRNA determination18.…”

Berberis Vulgaris and Berberine: An Update Review

“…Berberine shows anti‐apoptotic effects against ischemia by decreasing HIF‐1α, caspase 9, caspase 3, and increasing Bcl‐2/Bax ratio (Zhang et al ., ) and by the increased phosphor‐activation of Akt (higher p‐Akt to total Akt), (Hu et al ., ; Kim et al ., ; Simoes Pires et al ., ; Zhang et al ., ). Berberine can inhibit the degradation of retinoblastoma mRNA through its function on the poly (A) tail which avoids cells entering in the apoptotic process (Chai et al ., ). However, pro‐apoptosis by berberine under hypoxia also has been reported (Cui et al ., ), and it seems that berberine regulates neuronal apoptosis in cerebral ischemia, which might be dependent on the degree of cell injury (Zhang et al ., ).…”

Berberine: Pathways to protect neurons

“…It is found that BBR could prolong half‐life of mRNA of the retinoblastoma 1 by acting on the poly(A) tail. Therefore, BBR facilitates cell cycle arrest of neurons and ultimately avoids apoptosis in the ischemia/reperfusion model (Chai et al, ). A recent study also showed that BBR inhibits the expression of cyclin D1 and p53 at the onset of reperfusion to keep the cell in the G0/G1 phase.…”