These data are in full agreement with previous findings demonstrating that HSV 1 has the potential to elicit various forms of cell death, including necrosis, apoptosis, anoikis and autophagy. Compelling evidence has accumulated that the various p63 isoforms play pivotal roles in several physiological and pathological processes of the selleck chemical Axitinib ocular surface. The N and TA p63 subclasses operate in a concerted fashion to maintain the proliferative potential of the ocu lar surface Inhibitors,Modulators,Libraries epithelia and to control the processes of differ entiation and regeneration in the conjunctiva and cornea. The ocular Inhibitors,Modulators,Libraries surface may be exposed to harmful environmental stimuli, such as ultraviolet exposure, and may also function as an entry site for a wide array of human pathogenic microorganisms.
By disturbing the delicate balance between the pro survival N and the pro apoptotic TA isoforms, stress signals that alter the expression of p63 may cause profound alterations in the viability of the ocular cells Inhibitors,Modulators,Libraries and in the tissue homeostasis of the ocular surface. As a step in our investigations Inhibitors,Modulators,Libraries of the underlying molecular events implicated in HSV 1 induced ocular cytopathogenicity, we focused on the role of p63 in the SIRC cell line. Our experiments revealed the constitutive expression of Np63 in the mock infected SIRC cells. Interestingly, we observed an impres sive reduction in the level of the Np63 and a dramatic rise in the level of TAp63�� following infection with HSV 1. The kinetics of HSV 1 replication and the level of TAp63�� expression correlated strictly.
Note worthy previous studies Inhibitors,Modulators,Libraries raise the possibility that HSV 1 may alter the expression of p63 via multiple mechanisms. Certain viral proteins may have the potential to alter the transcription of p63 or to affect the stability and activity of the p63 isoforms via the induction of their posttranslational modifications. The virion asso ciated host shutoff protein, which causes the degradation selleckchem Nintedanib of cellular and viral RNA, may evoke a decrease in the level of Np63 mRNA. The trans inducing factor, which stimulates the transcription of IE genes via cellular transcription factors, such as the POU homeodomain protein Oct 1 and the host cell factor, may elicit an increase in the level of TAp63��. The infected cell protein 0, which controls the stability of cellular proteins and leads to the disruption of promyelocytic leu kemia nuclear bodies, may dysregulate the expression pattern of p63. How ever, interesting studies have demonstrated that the repli cation of HSV 1 DNA activates the ataxia teleangiectasia mutated dependent signaling pathway implicated in the cellular DNA damage response.
Related posts: