हमारा समूह 1000 से अधिक वैज्ञानिक सोसायटी के सहयोग से हर साल संयुक्त राज्य अमेरिका, यूरोप और एशिया में 3000+ वैश्विक सम्मेलन श्रृंखला कार्यक्रम आयोजित करता है और 700+ ओपन एक्सेस जर्नल प्रकाशित करता है जिसमें 50000 से अधिक प्रतिष्ठित व्यक्तित्व, प्रतिष्ठित वैज्ञानिक संपादकीय बोर्ड के सदस्यों के रूप में शामिल होते हैं।
ओपन एक्सेस जर्नल्स को अधिक पाठक और उद्धरण मिल रहे हैं
700 जर्नल और 15,000,000 पाठक प्रत्येक जर्नल को 25,000+ पाठक मिल रहे हैं
Jamilur R. Talukder, Jaleesa Wright, Antara Jaima, Deja McIntosh
Background: Varieties of inflammatory cytokines are produced during chronic enteritis including inflammatory bowel disease (IBD), that leads to malabsorption of nutrients and diarrhea. The inflammatory mediators are produced from different tissues of the body. Arachidonic acid metabolite derived via Lipoxygenase pathway, leukotriene D4 (LT) inhibits Na+-dependent alanine (Ala) cotransport (ASCT1, solute carrier, slc1a4) in the apical membrane of enterocytes by decreasing the affinity of cotransporter. However, the intracellular mechanism of LT-mediated inhibition of ASCT1 activity is unknown.
Objective:To investigate the intracellular mechanism of leukotriene D4 (LT) mediated inhibition of ASCT1 activity in enterocytes.
Methods: Rat intestinal epithelial cells (IEC-6) were grown on transwell plates. [3H]-Ala uptake was measured in 10 days postconfluent cells using a scintillation counter. IEC-6 cells were treated with different inhibitors in 8 days postconfluent to intercept different checkpoints of pathways for LT-mediated inhibition of ASCT1 activity. Intracellular Ca2+ and cAMP levels were measured. Immunoblotting, qRT-PCR, and immunocytochemistry were performed following the standard protocols.
Results: LT treatment increased more than 2.5-fold [(cAMP)i] and [(Ca2+ )i]. PKA, PKC-δ and -θ inhibitor did not reverse the LT-mediated inhibition of ASCT1 activity. However, PKC-α inhibitor antagonized LT effect on ASCT1 activity. Further downstream of PKC-α pathway, tyrosine kinase (Akt) inhibitor also reversed LT-mediated inhibition of ASCT1 activity. Immunoblotting, qRT-PCR, immunocytochemistry, and Kinetics studies demonstrated that the mechanism of decreased affinity of ASCT1 by LT was due to decrease in affinity of ASCT1 for Ala transport that was restored by Akt inhibitor.
Conclusion: Therefore, we conclude that LT inhibits ASCT1 activity by decreasing the affinity of ASCT1 to Ala through Ca2+-dependent PKCα-Akt pathway in enterocytes.