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921.
Sio SW Ang SF Lu J Moochhala S Bhatia M 《Journal of immunology (Baltimore, Md. : 1950)》2010,185(10):6265-6276
Acute lung injury (ALI) is a major cause of mortality in burn patients, even without direct inhalational injury. Identification of early mediators that instigate ALI after burn and of the molecular mechanisms by which they work are of high importance but remain poorly understood. We previously reported that an endogenous neuropeptide, substance P (SP), via binding neurokinin-1 receptor (NK1R), heightens remote ALI early after severe local burn. In this study, we examined the downstream signaling pathway following SP-NK1R coupling that leads to remote ALI after burn. A 30% total body surface area full-thickness burn was induced in male BALB/c wild-type (WT) mice, preprotachykinin-A (PPT-A) gene-deficient mice, which encode for SP, and PPT-A(-/-) mice challenged with exogenous SP. Local burn injury induced excessive SP-NK1R signaling, which activated ERK1/2 and NF-κB, leading to significant upregulation of cyclooxygenase (COX)-2, PGE metabolite, and remote ALI. Notably, lung COX-2 levels were abrogated in burn-injured WT mice by L703606, PD98059, and Bay 11-7082, which are specific NK1R, MEK-1, and NF-κB antagonists, respectively. Additionally, burn-injured PPT-A(-/-) mice showed suppressed lung COX-2 levels, whereas PPT-A(-/-) mice injected with SP showed augmented COX-2 levels postburn, and administration of PD98059 and Bay 11-7082 to burn-injured PPT-A(-/-) mice injected with SP abolished the COX-2 levels. Furthermore, treatment with parecoxib, a selective COX-2 inhibitor, attenuated proinflammatory cytokines, chemokines, and ALI in burn-injured WT mice and PPT-A(-/-) mice injected with SP. To our knowledge, we show for the first time that SP-NK1R signaling markedly elevates COX-2 activity via ERK1/2 and NF-κB, leading to remote ALI after burn. 相似文献
922.
Jixian Luo Tingshuang Xu Xiaoguang Wang Xueqing Ba Xue Feng Vishwa Deepak Xianlu Zeng 《Journal of cellular biochemistry》2010,110(4):910-919
L‐selectin and P‐selectin glycoprotein ligand‐1 (PSGL‐1) are adhesion molecules that play critical roles in neutrophil rolling during inflammation and lymphocyte homing. On the other hand they also function as signaling receptors to induce cytoskeleton changes. The present study is to investigate the signaling kinases responsible for the F‐actin changes mediated by L‐selectin and PSGL‐1 during neutrophil rolling on E‐selectin. Western blot analysis demonstrated that PI3K activation, peaking within 5 min, was induced by ligation of L‐selectin and PSGL‐1 with E‐selectin, and that Vav1 (the pivotal downstream effector of PI3K signaling pathway involved in cytoskeleton regulation) was recruited to the membrane and tyrosine‐phosphorylated, depending on PI3K. Furthermore, the F‐actin redistribution and assembly mediated by ligation with E‐selectin were blocked by LY294002, a PI3K specific inhibitor. Additional experiments showed that PI3K activity was involved in neutrophil rolling on E‐selectin. However, Syk/Zap70, the well‐known upstream kinase of PI3K, was not involved in this event. These data suggest that PI3K is required for the F‐actin‐based cytoskeleton changes during neutrophil rolling on E‐selectin, which may consequently regulate the rolling event. J. Cell. Biochem. 110: 910–919, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
923.
Che‐Chung Yeh Hongzhe Li Deepak Malhotra Sally Turcato Susan Nicholas Richard Tu Bo‐Qing Zhu John Cha Philip M Swigart Bat‐Erdene Myagmar Anthony J. Baker Paul C. Simpson Michael J. Mann 《Journal of cellular biochemistry》2010,109(6):1185-1191
Global activation of MAP kinases has been reported in both human and experimental heart failure. Chronic remodeling of the surviving ventricular wall after myocardial infarction (MI) involves both myocyte loss and fibrosis; we hypothesized that this cardiomyopathy involves differential shifts in pro‐ and anti‐apoptotic MAP kinase signaling in cardiac myocyte (CM) and non‐myocyte. Cardiomyopathy after coronary artery ligation in mice was characterized by echocardiography, ex vivo Langendorff preparation, histologic analysis and measurements of apoptosis. Phosphorylation (activation) of signaling molecules was analyzed by Western blot, ELISA and immunohistochemistry. Post‐MI remodeling involved dramatic changes in the phosphorylation of both stress‐activated MAP (SAP) kinase p38 as well as ERK, a known mediator of cell survival, but not of SAP kinase JNK or the anti‐apoptotic mediator of PI3K, Akt. Phosphorylation of p38 rose early after MI in the infarct, whereas a more gradual rise in the remote myocardium accompanied a rise in apoptosis in that region. In both areas, ERK phosphorylation was lowest early after MI and rose steadily thereafter, though infarct phosphorylation was consistently higher. Immunostaining of p‐ERK localized to fibrotic areas populated primarily by non‐myocytes, whereas staining of p38 phosphorylation was stronger in areas of progressive CM apoptosis. Relative segregation of CMs and non‐myocytes in different regions of the post‐MI myocardium revealed signaling patterns that imply cell type‐specific changes in pro‐ and anti‐apoptotic MAP kinase signaling. Prevention of myocyte loss and of LV remodeling after MI may therefore require cell type‐specific manipulation of p38 and ERK activation. J. Cell. Biochem. 109: 1185–1191, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
924.
Deepti Sharma Raman K. Sharma Sumati Bhatia Rakesh Tiwari Deendayal Mandal Jessica Lehmann Keykavous Parang Carl E. Olsen Virinder S. Parmar Ashok K. Prasad 《Biochimie》2010
A series of 3-(N-alkyl-N-phenylamino)propan-2-ol derivatives were synthesized from epichlorohydrine in a multi-step strategy and were evaluated as Src kinase inhibitors. First, epoxy ring opening of epichlorohydrine was carried out in the presence of N-alkylanilines to yield 3-(N-alkyl-N-phenylamino)-1-chloro-propan-2-ol derivatives using Ca(OTf)2 as catalyst based on our previous studies [1]. Second, ring closure was performed under basic conditions to afford N-epoxymethyl N-alkylaniline derivatives. Finally, the epoxide ring opening with four different secondary amines and three nucleobases afforded the final products, i.e., a series of β-amino alcohols. All compounds were screened for their inhibitory activity against Src kinase and anticancer activity on human breast carcinoma cells, BT-20 cell line. Among all compounds, 3-N-methyl-N-phenylamino-1-(pyrrolidin-1-yl)propan-2-ol (13b) exhibited the highest inhibitory potency (IC50 = 66.1 μM) against Src kinase. Structure-activity relationship studies suggested that the incorporation of bulky groups at position 1 and N-substitution with groups larger than methyl moiety, reduced the inhibitory potency of the compound significantly. Compounds 3-(N-ethyl-N-phenylamino-)-1-(4-methylpiperazin-1-yl)propan-2-ol (14c) and 3-(N-ethyl-N-phenylamino)-1-(thymine-1-yl)propan-2-ol (17) were found to inhibit the growth of breast carcinoma cells by approximately 45–49% at concentration of 50 μM. 相似文献
925.
926.
Avdhoot D. Velankar Gianluca Quintini Arati Prabhu Alexander Weber Gundula Hunaeus Britta Voland Monika Wuest Christian Orjeda Dipak Harel Shaji Varghese Vikas Gore Meenal Patil Deepak Gayke Matthias Herdemann Isabelle Heit Andrea Zaliani 《Bioorganic & medicinal chemistry》2010,18(12):4547-4559
Interleukin-2 inducible T-cell kinase (ITK) is one of five kinases that belong to the Tec kinase family that plays an important role in T-cell and mast cell signaling. Various reports point to a role of ITK in the treatment of allergic asthma. For example, it was shown that mice lacking ITK have reduced airway hyperresponsiveness, inflammation and tracheal responses in an allergic asthma model. In this article, we disclose novel ITK inhibitors based on (4 or 5-aryl)pyrazolyl-indole scaffold that were also found to be selective for ITK over other kinases like IRK, CDK2, GSK3ß and PKA. 相似文献
927.
Semwal Ruchi Badoni Semwal Deepak Kumar Combrinck Sandra Viljoen Alvaro 《Phytochemistry Reviews》2020,19(4):761-785
Phytochemistry Reviews - Chromones are naturally occurring phenolic compounds that are universally present in a healthy human diet. To date, thousands of chromone derivatives, including chromone... 相似文献
928.
Nobuko Katoku-Kikyo Ellen Paatela Daniel L. Houtz Britney Lee Dane Munson Xuerui Wang Mohammed Hussein Jasmeet Bhatia Seunghyun Lim Ce Yuan Yoko Asakura Atsushi Asakura Nobuaki Kikyo 《The Journal of cell biology》2021,220(7)
Circadian rhythms regulate cell proliferation and differentiation, but circadian control of tissue regeneration remains elusive at the molecular level. Here, we show that proper myoblast differentiation and muscle regeneration are regulated by the circadian master regulators Per1 and Per2. Depletion of Per1 or Per2 suppressed myoblast differentiation in vitro and muscle regeneration in vivo, demonstrating their nonredundant functions. Both Per1 and Per2 were required for the activation of Igf2, an autocrine promoter of myoblast differentiation, accompanied by Per-dependent recruitment of RNA polymerase II, dynamic histone modifications at the Igf2 promoter and enhancer, and the promoter–enhancer interaction. This circadian epigenetic priming created a preferred time window for initiating myoblast differentiation. Consistently, muscle regeneration was faster if initiated at night, when Per1, Per2, and Igf2 were highly expressed compared with morning. This study reveals the circadian timing as a significant factor for effective muscle cell differentiation and regeneration. 相似文献
929.
Mahendran Ganesan Kumar Deepak Verma Sanjeet Kumar Chandran Ashish Warsi Zafar Iqbal Husain Zakir Afroz Shama Rout Prasant Kumar Rahman Laiq Ur 《Plant Cell, Tissue and Organ Culture》2021,146(1):161-170
Plant Cell, Tissue and Organ Culture (PCTOC) - Gymnemic acids (a group of triterpenoid saponins) found in Gymnema sylvestre (Retz.) R.Br. ex Sm. works as the main hypoglycaemic active components.... 相似文献
930.
Gopi M. Joyson Joe Jeevamani J. Goutham S. Simon Nina Tabitha Deepak Samuel V. Abhilash K. R. Robin R. S. Hariharan G. Muruganandam R. Krishnan P. Purvaja R. Ramesh R. 《Wetlands Ecology and Management》2021,29(5):653-668
Wetlands Ecology and Management - Coral reefs of Lakshadweep perform a range of vital ecosystem functions and sustain the livelihoods of island communities. Coral reefs provide ecosystem services... 相似文献