Role of calcium-independent phospholipase A2 in contraction of intrarenal artery smooth muscle / 中国药理学通报

Aim To investigate the role of calcium-independent phospholipase A2(iPLA2)in calcium regu-lation of intrarenal artery smooth muscle contraction.Methods The method of measuring the tension of isolated arterioles was used to explore the effect of bromoenol lactone(BEL), a specific inhibitor of iPLA2, on the tension of the intrarenal arteries in mice induced by different calcium channels, and the laser confocal calcium measurement technology was used to investigate the effect of BEL on the intracellular calcium influx mediated by arachidonic acid-mediated calcium channels.Results The intrarenal artery concentration dependent contractile response induced by the vasoconstrictors phenylephrine and 5-hydroxy tryptamine was inhibited by BEL(P<0.01).The contraction curve induced by CaCl2 was also inhibited by BEL(P<0.05).In the calcium-free K-H solution incubated with nifedipine, the intrarenal artery vasoconstriction caused by the release of sarcoplasmic reticulum calcium and the calcium influx of the SOC channel induced by CaCl2 was inhibited by BEL(P<0.05).BEL significantly inhibited the external calcium influx mediated by the ARC channel of human aortic smooth muscle cell lines incubated with nifedipine(P<0.01).Conclusions iPLA2 mediates the contractile response of intrarenal arteries by regulating the functions of L-type calcium channels, sarcoplasmic reticulum calcium release, SOC channels and ARC channels.

Involvement of Orai1 in tunicamycin-induced endothelial dysfunction

Endoplasmic reticulum (ER) stress is mediated by disturbance of Ca²⁺ homeostasis. The store-operated calcium (SOC) channel is the primary Ca²⁺ channel in non-excitable cells, but its participation in agent-induced ER stress is not clear. In this study, the effects of tunicamycin on Ca²⁺ influx in human umbilical vein endothelial cells (HUVECs) were observed with the fluorescent probe Fluo-4 AM. The effect of tunicamycin on the expression of the unfolded protein response (UPR)-related proteins BiP and CHOP was assayed by western blotting with or without inhibition of Orai1. Tunicamycin induced endothelial dysfunction by activating ER stress. Orai1 expression and the influx of extracellular Ca²⁺ in HUVECs were both upregulated during ER stress. The SOC channel inhibitor SKF96365 reversed tunicamycin-induced endothelial cell dysfunction by inhibiting ER stress. Regulation of tunicamycin-induced ER stress by Orai1 indicates that modification of Orai1 activity may have therapeutic value for conditions with ER stress-induced endothelial dysfunction.

Role of Ca2+ in hypoxic pulmonary vasoconstriction / 中华危重病急救医学

In acute hypoxia, pulmonary vascular will contract and divert blood to better ventilated area to optimize ventilation/perfusion matching, which is known as hypoxic pulmonary vasoconstriction (HPV). In chronic hypoxia, irreversible pulmonary vascular remodeling can be induced, characterized by pulmonary artery middle smooth muscle cells and the outer fiber cell hyperplasia in luminal stenosis and pulmonary artery hypertension (PAH) eventually. Furthermore, PAH can cause increased ventricular afterload, and right heart failure in severe cases. Pulmonary artery smooth muscle cell (PASMC) elevated Ca2+ concentration is one of the most important factors of its contractions, proliferation and migration. Recent studies on Ca2+ promoting in HPV were summarized in order to provide evidence for clinical prevention of hypoxia and therapeutic PAH.

Progress of STIM1, a dynamic calcium signal transducer, in cardiovascular diseases / 中国病理生理杂志

Stromal interaction molecule 1 (STIM1) is a transmembrane protein of the endoplasmic reticulum (ER) , a Ca2+ transducer in ER that activates the store-operated calcium channel.Through Orai1 protein, STIM1 adjusts the intracellular and extracellular calcium concentration.This way is called a store-operated Ca2+ entry.STIM1 plays a key role in phenotypic transformation of vascular smooth muscle cells, proliferation of endothelial cells, myocardial hypertrophy and myocardial fibrosis to regulate lots of cardiovascular diseases, such as atherosclerosis, congestive heart failure and systemic hypertension.STIM1 is closely related to cardiovascular diseases through calcium signal.The research progress of STIM1 in cardiovascular diseases is mainly discussed in this article.

Initiation Site of Ca2+ Entry Evoked by Endoplasmic Reticulum Ca2+ Depletion in Mouse Parotid and Pancreatic Acinar Cells

PURPOSE: In non-excitable cells, which include parotid and pancreatic acinar cells, Ca(2+) entry is triggered via a mechanism known as capacitative Ca(2+) entry, or store-operated Ca(2+) entry. This process is initiated by the perception of the filling state of endoplasmic reticulum (ER) and the depletion of internal Ca(2+) stores, which acts as an important factor triggering Ca(2+) entry. However, both the mechanism of store-mediated Ca(2+) entry and the molecular identity of store-operated Ca(2+) channel (SOCC) remain uncertain. MATERIALS AND METHODS: In the present study we investigated the Ca(2+) entry initiation site evoked by depletion of ER to identify the localization of SOCC in mouse parotid and pancreatic acinar cells with microfluorometeric imaging system. RESULTS: Treatment with thapsigargin (Tg), an inhibitor of sarco/endoplasmic reticulum Ca(2+)-ATPase, in an extracellular Ca(2+) free state, and subsequent exposure to a high external calcium state evoked Ca(2+) entry, while treatment with lanthanum, a non-specific blocker of plasma Ca(2+) channel, completely blocked Tg-induced Ca(2+) entry. Microfluorometric imaging showed that Tg-induced Ca(2+) entry started at a basal membrane, not a apical membrane. CONCLUSION: These results suggest that Ca2+ entry by depletion of the ER initiates at the basal pole in polarized exocrine cells and may help to characterize the nature of SOCC.

Effects of 2-APB on Store-operated Ca2+ Channel Currents of Hepatocytes after Hepatic Ischemia/Reperfusion Injury in Rats / 华中科技大学学报（医学）（英德文版）

The effects of hepatic ischemia/reperfusion (I/R) injuries on hepatocellular viability and store-operated calcium current (Isoc) in isolated rat hepatocytes and the effects of 2-APB on storeoperated calcium current (Isoc) in isolated rat hepatocytes after hepaticischemia/reperfusion injuries were studied. Hepatic ischemia and reperfusion injury model was established and whole cell patch-clamp techniques were used to investigate the effects of 2-APB on Isoc. The results showed that ischemia/reperfusion injuries could significantly reduce hepatocellular viability and further increase Isoc in hepatocytes and 2-APB (20, 40, 60, 80, 100 μmol/L) produced a concentration-dependent decrease of Isoc with IC50 value of 64.63±10.56 μmol/L (n= 8). It was concluded that ischemia/reperfusion injuries could reduce hepatocellular viability, probably through increased Isoc in hepatocytes and 2-APB had a protective effect on ischemia/reperfusion-induced liver injury, probably though inhibiting Isoc.