CD38 produces nicotinic acid adenosine dinucleotide phosphate in the lysosome.

Nicotinic acid adenosine dinucleotide phosphate (NAADP) is a Ca2+-mobilizing second messenger that regulates a wide range of biological activities. However, the mechanism of its biogenesis remains controversial. CD38 is the only enzyme known to catalyze NAADP synthesis from NADP and nicotinic acid. CD38-mediated catalysis requires an acidic pH, suggesting that NAADP may be produced in acidic endolysosomes, but this hypothesis is untested. In this study, using human cell lines, we specifically directed CD38 to the endolysosomal system and assessed cellular NAADP production. First, we found that nanobodies targeting various epitopes on the C-terminal domain of CD38 could bind to cell surface-localized CD38 and induce its endocytosis. We also found that CD38 internalization occurred via a clathrin-dependent pathway, delivered CD38 to the endolysosome, and elevated intracellular NAADP levels. We also created a CD38 variant for lysosome-specific expression, which not only withstood the degradative environment in the lysosome, but was also much more active than WT CD38 in elevating cellular NAADP levels. Supplementing CD38-expressing cells with nicotinic acid substantially increased cellular NAADP levels. These results demonstrate that endolysosomal CD38 can produce NAADP in human cells. They further suggest that CD38's compartmentalization to the lysosome may allow for its regulation via substrate access, rather than enzyme activation, thereby providing a reliable mechanism for regulating cellular NAADP production.

[Study on propofol and fentanyl administrated via common carotid artery in rabbits].

OBJECTIVE: To compare the pharmacodynamic differences of common carotid artery administration with ear vein administration of propofol and fentanyl in rabbits. METHODS: Sixty New Zealand white rabbits were randomly divided into four groups(n = 15):PvFv, PvFa, PaFv and PaFa groups. Propofol 30 mg×kg(-1)×h(-1) and fentanyl 2 µg×kg(-1)×h(-1)were administrated via the ear vein or the common carotid artery. The outcomes were recorded, including the time of consciousness loss and recovery, to electrocerebral silence, dose of propofol and fentanyl, mean arterial pressure, heart rate, respiration rate and SpO2. RESULTS: (1) None of rabbits appeared breathing to be depressed seriously in group PaFa, while respiratory in the other groups were significantly depressed. (2) The dosage of propofol and fentanyl of group PaFa was significantly less than the other groups (P < 0.05). (3) The time of consciousness loss and recovery of group PaFa were shorter than the other three groups. CONCLUSION: Compared to drugs infusion via the ear vein, infusion of propol and fentanyl via the common carotid artery is more advantageous in some aspects, such as rapid anesthesia induction and recovery, smaller dose, and smaller impact on the hemodynamic and respiratory.

[Effects of depressive disorder on monocytic expression of CD(40) and plasma IL-8 concentration in senile coronary heart disease patients].

OBJECTIVE: To observe the monocytic expression of CD(40) and plasma IL-8 concentration in senile CHD (coronary heart disease) patients with depressive disorder and examine the effects of immunological factors in depressive disorder and CHD. METHODS: A total of 100 senile CHD patients (> 60 yr old) were divided into 3 group: control group (A, n = 30), depression score ≤ 20 & anxiety score ≤ 6; therapy group (B, n = 35), depression score ≥ 30 & anxiety score ≤ 6, psychological evaluations with HAMD (Hamilton depression rating scale) from Day 1 pre-operation to Day 7 post-operation; non-therapy group (C, n = 35), depression score ≥ 30 & anxiety score ≤ 6. They underwent the same operation: lumbar decompression & fusion, stripping of great saphenous vein and repair of indirect hernia. At Day 1 pre-operation and Day 7 post-operation, 2 ml venous blood was drawn for the detection of monocytic expression of CD(40) and plasma concentration of IL-8 (interleukin-8). RESULTS: Depressive value of Group B at post-operation was lower than that at pre-operation and Group C ((25.1 ± 2.9) vs (33.2 ± 1.4) & (34.2 ± 0.8), P < 0.05); the pre-operative expression of CD(40) of Group A was lower than the other groups ((123 ± 18) vs (197 ± 23) & (204 ± 26), P < 0.05). And Group B at post-operation was lower than Group C ((147 ± 19) vs (212 ± 18), P < 0.05); the pre-operative concentration of IL-8 was lowest in Group A ((85 ± 16) ng/L vs (151 ± 18) ng/L & (164 ± 22) ng/L, P < 0.05). And Group B at post-operation was lower than Group C ((158 ± 19) ng/L vs (197 ± 24) ng/L, P < 0.05). There were significantly positive correlations between depression scores, the expression of CD(40) and the plasma concentration of IL-8. CONCLUSION: Depressive disorders elevate the monocytic expression of CD(40) and raise the plasma concentration of IL-8 in senile CHD patients. Some immunological factors may play a important role in depressive disorder and CHD.