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Zenas George Yusuf Omosun Anthony A. Azenabor Jason Goldstein James Partin Kahaliah Joseph Debra Ellerson Qing He Francis Eko Melissa A. McDonald Matthew Reed Pavel Svoboda Olga Stuchlik Jan Pohl Erika Lutter Claudiu Bandea Carolyn M. Black Joseph U. Igietseme 《Biochemical and biophysical research communications》2019,508(2):421-429
The unfolded protein response (UPR) contributes to chlamydial pathogenesis, as a source of lipids and ATP during replication, and for establishing the initial anti-apoptotic state of host cell that ensures successful inclusion development. The molecular mechanism(s) of UPR induction by Chlamydia is unknown. Chlamydia use type III secretion system (T3SS) effector proteins (e.g, the Translocated Actin-Recruiting Phosphoprotein (Tarp) to stimulate host cell's cytoskeletal reorganization that facilitates invasion and inclusion development. We investigated the hypothesis that T3SS effector-mediated assembly of myosin-II complex produces activated non-muscle myosin heavy chain II (NMMHC-II), which then binds the UPR master regulator (BiP) and/or transducers to induce UPR. Our results revealed the interaction of the chlamydial effector proteins (CT228 and Tarp) with components of the myosin II complex and UPR regulator and transducer during infection. These interactions caused the activation and binding of NMMHC-II to BiP and IRE1α leading to UPR induction. In addition, specific inhibitors of myosin light chain kinase, Tarp oligomerization and myosin ATPase significantly reduced UPR activation and Chlamydia replication. Thus, Chlamydia induce UPR through T3SS effector-mediated activation of NMMHC-II components of the myosin complex to facilitate infectivity. The finding provides greater insights into chlamydial pathogenesis with the potential to identify therapeutic targets and formulations. 相似文献
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For malignant cells cultured from a human astrocytoma, electrophysiological characteristics of the plasma membrane included specific resistivity of 446.82 ± 279.5 ohm·cm2, specific capacitance of 0.758 ± 0.52 microfarads/cm2, time constant 0.318± 0.10 msec. The resting membrane potential averaged-14.07 ± 7.4 mV; the mean input resistance 8.1 ± 4.0 megohms. The average cell area was 1638 ± 585 ±2 for contactual and 1919 ± 989 ±2 for noncontactual cells. Changes in input resistance and resting membrane potential were observed with increasing time in culture, possibly reflecting cell cycling. There did not appear to be electrical coupling in this cell line. 相似文献
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S D Brain R D Camp A K Black P M Dowd M W Greaves A W Ford-Hutchinson S Charleson 《Prostaglandins》1985,29(4):611-619
Chemoattractant arachidonate lipoxygenase products have been recovered from the skin lesions of psoriasis, and may play a role in eliciting the intra-epidermal neutrophil infiltrate that characterises this disease. In view of evidence for lipoxygenase activity in psoriasis, the characteristic vasodilation in psoriatic lesions, and the vasodilator properties of leukotriene (LT) C4 and D4 in human skin, the presence of these LTs in psoriatic lesions has been investigated. Skin chamber fluid from abraded psoriatic lesions contained significantly greater amounts of immunoreactive material than that from clinically normal skin, as determined by a double antibody radioimmunoassay (RIA) that uses antiserum cross-reacting with both LTC4 and LTD4. Purification of lesional chamber fluid and scale extracts by high performance liquid chromatography (HPLC) and RIA of fractions showed immunoreactivity which co-eluted with standard LTC4 and LTD4. These findings suggest that LTC4 and LTD4 may play a role in mediating the vasodilation and increased blood flow that characterise psoriatic skin lesions. 相似文献
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CTGF and SMADs, maintenance of scleroderma phenotype is independent of SMAD signaling 总被引:31,自引:0,他引:31
Holmes A Abraham DJ Sa S Shiwen X Black CM Leask A 《The Journal of biological chemistry》2001,276(14):10594-10601
160.
The review discusses the current field status of human and bovine trypanosomiases, and focuses on the molecular basis of innate and acquired control of African trypanosomes in people, cattle, and Cape buffalo. 相似文献