scholarly journals The Role of CagA Protein Signaling in Gastric Carcinogenesis — CagA Signaling in Gastric Carcinogenesis

Author(s):  
Stephanie E. ◽  
Eduardo Mucito-Varela ◽  
German Ruben ◽  
Yolanda Lopez-Vidal ◽  
Gonzalo Castillo-Rojas

Author(s):  
Ki-Baik Hahm ◽  
Ho-Yeong Lim ◽  
Seonghyang Sohn ◽  
Hyuk-Jae Kwon ◽  
Ki-Myung Lee ◽  
...  
Keyword(s):  


2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Sirui Guo ◽  
Jiahong Wang ◽  
Huarong Xu ◽  
Weiwei Rong ◽  
Cheng Gao ◽  
...  

Alzheimer’s disease (AD) is a widespread neurodegenerative disease caused by complicated disease-causing factors. Unsatisfactorily, curative effects of approved anti-AD drugs were not good enough due to their actions on single-target, which led to desperate requirements for more effective drug therapies involved in multiple pathomechanisms of AD. The anti-AD effect with multiple action targets of Kai-Xin-San (KXS), a classic prescription initially recorded in Bei Ji Qian Jin Yao Fang and applied in the treatment of dementia for thousands of years, was deciphered with modern biological methods in our study. Aβ25-35 and D-gal-induced AD rats and Aβ25-35-induced PC12 cells were applied to establish AD models. KXS could significantly improve cognition impairment by decreasing neurotransmitter loss and enhancing the expression of PI3K/Akt. For the first time, KXS was confirmed to improve the expression of PI3K/Akt by neurotransmitter 5-HT. Thereinto, PI3K/Akt could further inhibit Tau hyperphosphorylation as well as the apoptosis induced by oxidative stress and neuroinflammation. Moreover, all above-mentioned effects were verified and blocked by PI3K inhibitor, LY294002, in Aβ25-35-induced PC12 cells, suggesting the precise regulative role of KXS in the PI3K/Akt pathway. The utilization and mechanism elaboration of KXS have been proposed and dissected in the combination of animal, molecular, and protein strategies. Our results demonstrated that KXS could ameliorate AD by regulating neurotransmitter and PI3K/Akt signal pathway as an effective multitarget treatment so that the potential value of this classic prescription could be explored from a novel perspective.



2017 ◽  
Vol 121 (6) ◽  
pp. 636-649 ◽  
Author(s):  
Xiaolong Zhu ◽  
Sha Ding ◽  
Cong Qiu ◽  
Yanna Shi ◽  
Lin Song ◽  
...  

Rationale: The highly conserved NOTCH (neurogenic locus notch homolog protein) signaling pathway functions as a key cell–cell interaction mechanism controlling cell fate and tissue patterning, whereas its dysregulation is implicated in a variety of developmental disorders and cancers. The pivotal role of endothelial NOTCH in regulation of angiogenesis is widely appreciated; however, little is known about what controls its signal transduction. Our previous study indicated the potential role of post-translational SUMO (small ubiquitin-like modifier) modification (SUMOylation) in vascular disorders. Objective: The aim of this study was to investigate the role of SUMOylation in endothelial NOTCH signaling and angiogenesis. Methods and Results: Endothelial SENP1 (sentrin-specific protease 1) deletion, in newly generated endothelial SENP1 (the major protease of the SUMO system)–deficient mice, significantly delayed retinal vascularization by maintaining prolonged NOTCH1 signaling, as confirmed in cultured endothelial cells. An in vitro SUMOylation assay and immunoprecipitation revealed that when SENP1 associated with N1ICD (NOTCH1 intracellular domain), it functions as a deSUMOylase of N1ICD SUMOylation on conserved lysines. Immunoblot and immunoprecipitation analyses and dual-luciferase assays of natural and SUMO-conjugated/nonconjugated NOTCH1 forms demonstrated that SUMO conjugation facilitated NOTCH1 cleavage. This released N1ICD from the membrane and stabilized it for translocation to the nucleus where it functions as a cotranscriptional factor. Functionally, SENP1-mediated NOTCH1 deSUMOylation was required for NOTCH signal activation in response to DLL4 (Delta-like 4) stimulation. This in turn suppressed VEGF (vascular endothelial growth factor) receptor signaling and angiogenesis, as evidenced by immunoblotted signaling molecules and in vitro angiogenesis assays. Conclusions: These results establish reversible NOTCH1 SUMOylation as a regulatory mechanism in coordinating endothelial angiogenic signaling; SENP1 acts as a critical intrinsic mediator of this process. These findings may apply to NOTCH-regulated biological events in nonvascular tissues and provide a novel therapeutic strategy for vascular diseases and tumors.



1995 ◽  
Vol 35 (1-2) ◽  
pp. 59-64 ◽  
Author(s):  
Pelayo Correa




2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Patricia Schneider ◽  
Diane Slusarski ◽  
Douglas Houston


2019 ◽  
Vol 38 (9) ◽  
pp. 1591-1597 ◽  
Author(s):  
Paulo Pimentel de Assumpção ◽  
Taíssa Maíra Thomaz Araújo ◽  
Paula Baraúna de Assumpção ◽  
Williams Fernandes Barra ◽  
André Salim Khayat ◽  
...  


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