Recent studies showed that atherosclerosis is a lysosomal storage disease (LSD) and
Niemann-Pick disease type C1 (NPC1) is the most important protein of the lysosomal membrane
最近的研究表明,動脈粥樣硬化是溶酶體貯積病(LSD),而Niemann-Pick病C1型(NPC1)
是溶酶體膜中最重要的蛋白質
However, NPC1 gene expression showed positive significant correlation with IL-10 serum concentration (p = 0.04, r = 0.29).
然而,NPC1基因表達與IL-10血清濃度呈顯著正相關(p = 0.04,r = 0.29)。
We also observed lower serum concentration of IL-10 in the subjects with lower
25-hydroxyvitamin D serum concentration (p = 0.034).
我們還觀察到具有較低25-羥基維生素D(25-OH-D)血清濃度的受試者中較低的血清IL-10濃度(p = 0.034)。
Niemann-Pick disease, type C1 (NPC1)
尼曼匹克病,C1型(NPC1)
We found increased levels of interleukin 3, chemokine (C-X-C motif) ligand 5, interleukin 16 and chemokine ligand 3 (CCL3), and decreased levels of interleukin 4, 10, 13 and 12p40 in CSF from NPC1 patients.
我們發現來自NPC1患者的腦脊液中白細胞介素IL-4,IL-10,IL-12p40的水平降低。
能提高IL-4的元素:鋅、維生素A
能提高IL-10的元素:鋅、錳、硒、維生素A、維生素D、維生素E
上方導讀已經說明ATP7B跟錳有關了,所以影響NPC1基因表達的也許是鋅。
These results suggest that NPC1 influnces ATP7B-mediated transport of Cu into Golgi in the liver.
這些結果表明,NPC1影響ATP7B介導的Cu向肝臟中的高爾基體的轉運。
These studies suggest that NPC1 is involved in liver Cu metabolism.
這些研究表明NPC1參與肝臟Cu代謝。
Contrary to these observations, we show that LPS-induced IL-12p40 production in human monocytic
cells is positively regulated by the calcium pathway
與這些觀察結果相反,我們表明LPS誘導的人單核細胞中IL-12p40的產生受鈣的正調控
the decreased lysosomal acidity may result in the depletion of Ca2+ in lysosomes ,
a critical source of Ca2+ for cholesterol transport out of lysosomes.
溶酶體酸度的降低可能導致溶酶體中Ca2 +的消耗,這是把膽固醇從溶酶體轉運出來的Ca2+(鈣)的關鍵來源。
三、
The liver (24 ± 2%; p < 0.0001) and the lung (28 ± 6%; p < 0.0001) of
Npc1−/− mice were markedly decreased in zinc
Npc1-/-小鼠的肝臟(24±2%; p <0.0001)和肺(28±6%; p <0.0001)的鋅顯著降低
In contrast, there was a reduction in the Npc1−/− mouse liver (14 ± 2%; p < 0.0001)
and lung (15 ± 6%; p = 0.02) manganese concentration.
相反,Npc1-/-小鼠肝臟(14±2%; p <0.0001)和肺(15±6%; p = 0.02)錳濃度降低。
Vitamin D3 increases mRNA and protein expression of the ZnT10 transporter.
Vitamin D3 appears to be important for zinc and manganese homeostasis.
維生素D3增加ZnT10轉運蛋白的mRNA和蛋白質表達。維生素D3似乎對鋅和錳的穩態很重要。
不知肝臟的缺鋅錳和缺少維它命D有沒有關係?
四、
Niemann–Pick disease type C1 is a sphingosine storage disease that
causes deregulation of lysosomal calcium
Niemann-Pick病C1型是一種引起溶酶體鈣失調的鞘氨醇貯積病
鞘氨醇能被鞘氨醇激酶磷酸 化為 S-1-P。生成的 S-1-P 可被脂質磷酸鹽磷酸酶
(lipid phosphate phosphatase, LPP) 及 S-1-P 磷酸酶(sphingosine-1-phosphate phosphatase, SPPase)
去磷酸化。 SPPase 催化產生的鞘氨醇能參與體內神經酰胺的補救合成途徑。此外,
S-1-P 還能被S-1-P 裂解酶(S1P lyase, SPL) 降解生成磷酸乙醇胺和十六碳醛,
最終經一系列酶降解為棕櫚酰-CoA, 進入甘油磷脂代謝通路。
For degradation, the sphingosine bases are phosphorylated to the corresponding
1-phospho derivatives (171-173); magnesium is required for this reaction
為了降解,將鞘氨醇鹼基磷酸化為相應的1-磷酸衍生物(171-173); 該反應需要鎂
Vitamin B6 (pyridoxine) is required for S1P lyase activity.
維生素B6(吡哆醇)是S1P裂解酶活性所必需的。
S1P lyase requires vitamin B6 as a co-factor for the degradation of S1P (37)
S1P裂解酶需要維生素B6作為S1P降解的輔助因子
This role of ABCG5/ ABCG8 in cholesterol transport has been confirmed
ABCG5 / ABCG8在膽固醇轉運中的作用已得到證實
ABCG5 and ABCG8 form an obligate heterodimer that mediates Mg2+- and ATP-dependent
sterol transport across the cell membrane (PubMed:27144356).
ABCG5和ABCG8形成專性異二聚體,其介導穿過細胞膜的Mg2+(鎂離子)-和ATP依賴性固醇轉運(PubMed:27144356)。
鎂有助於膽固醇轉運,代表鎂能減少膽固醇累積。