Up-regulation of Cholesterol Absorption Is a Mechanism for Cholecystokinin-induced Hypercholesterolemia

Zhou, Lichun; Hong, Yun–Chul; Okoro, Emmanuel U.; Guo, ZhongMao

doi:10.1074/jbc.m113.534388

Cited by 15 publications

(8 citation statements)

References 42 publications

(74 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…B). Various studies suggest that the immediate downstream mediator of G βγ is PI3K . To examine the role of PI3K in the melatonin‐induced response, we tested the PI3K inhibitor wortmannin.…”

Section: Resultsmentioning

confidence: 99%

Melatonin‐mediated inhibition of Purkinje neuron P‐type Ca²⁺ channels in vitro induces neuronal hyperexcitability through the phosphatidylinositol 3‐kinase‐dependent protein kinase C delta pathway

Zhang

et al. 2015

Journal of Pineal Research

View full text Add to dashboard Cite

Although melatonin receptors are widely expressed in the mammalian central nervous system and peripheral tissues, there are limited data regarding the functions of melatonin in cerebellar Purkinje cells. Here, we identified a novel functional role of melatonin in modulating P-type Ca(2+) channels and action-potential firing in rat Purkinje neurons. Melatonin at 0.1 μm reversibly decreased peak currents (I(Ba)) by 32.9%. This effect was melatonin receptor 1 (MT(R1)) dependent and was associated with a hyperpolarizing shift in the voltage dependence of inactivation. Pertussis toxin pretreatment, intracellular application of QEHA peptide, and a selective antibody raised against the Gβ subunit prevented the inhibitory effects of melatonin. Pretreatment with phosphatidylinositol 3-kinase (PI3K) inhibitors abolished the melatonin-induced decrease in I(Ba). Surprisingly, melatonin responses were not regulated by Akt, a common downstream target of PI3K. Melatonin treatment significantly increased protein kinase C (PKC) activity 2.1-fold. Antagonists of PKC, but not of protein kinase A, abolished the melatonin-induced decrease in I(Ba). Melatonin application increased the membrane abundance of PKCδ, and PKCδ inhibition (either pharmacologically or genetically) abolished the melatonin-induced IBa response. Functionally, melatonin increased spontaneous action-potential firing by 53.0%; knockdown of MT(R1) and blockade of P-type channels abolished this effect. Thus, our results suggest that melatonin inhibits P-type channels through MT(R1) activation, which is coupled sequentially to the βγ subunits of G(i/o)-protein and to downstream PI3K-dependent PKCδ signaling. This likely contributes to its physiological functions, including spontaneous firing of cerebellar Purkinje neurons.

show abstract

Section: Resultsmentioning

confidence: 99%

Melatonin‐mediated inhibition of Purkinje neuron P‐type Ca²⁺ channels in vitro induces neuronal hyperexcitability through the phosphatidylinositol 3‐kinase‐dependent protein kinase C delta pathway

Zhang

et al. 2015

Journal of Pineal Research

View full text Add to dashboard Cite

show abstract

“…NPC1L1 is downregulated by several dietary compounds including fat , cholesterol , fatty acids , calcium , curcumin , sitosterol , and lactobacillus from fermented foods , while dietary glucose was shown to increase its expression (84). NPC1L1 expression is also regulated by hormones: estrogen and cholecystokinin could increase it while peptide YY (PYY) reduced it . The effects of these factors are summarized in Table .…”

Section: Regulation Of Vitamin E Membrane Transport In the Intestinementioning

confidence: 99%

Vitamin E intestinal absorption: Regulation of membrane transport across the enterocyte

Reboul

2018

IUBMB Life

View full text Add to dashboard Cite

Vitamin E is an essential molecule for our development and health. It has long been thought that it was absorbed and transported through cellular membranes by a passive diffusion process. However, data obtained during the past 15 years showed that its absorption is actually mediated, at least in part, by cholesterol membrane transporters including the scavenger receptor class B type I (SR‐BI), CD36 molecule (CD36), NPC1‐like transporter 1 (NPC1L1), and ATP‐binding cassettes A1 and G1 (ABCA1 and ABCG1). This review focuses on the absorption process of vitamin E across the enterocyte. A special attention is given to the regulation of this process, including the possible competition with other fat‐soluble micronutrients, and the modulation of transporter expressions. Overall, recent results noticeably increased the comprehension of vitamin E intestinal transport, but additional investigations are still required to fully appreciate the mechanisms governing vitamin E bioavailability. © 2018 IUBMB Life, 71(4):416–423, 2019

show abstract

“…Data from studies indicate that Cholecystokinin increases cholesterol absorption by activation of a pathway comprising CCK1R/ CCK2R, Rab11a, Gβγ, PI3K, Akt, and NPC1L [26].…”

Section: Second Stage Of Cholesterol Absorptionmentioning

confidence: 99%

Association between Cholesterol Homeostasis with Intestinal Proteins, Enzymes and Drugs in Absorption of Cholesterol and its Relationship with Vascular Diseases: A Review

Javaid¹,

Khurshid²,

Munir³

2018

Biochem Pharmacol

View full text Add to dashboard Cite

The goal of this review is to discuss many aspects of cholesterol homeostasis in the body in order to presents the standards of cholesterol disposition and its levels, especially when several means might change the features of cholesterol synthesis and absorption and interrupt this equilibrium. With the detection of pathways of cholesterol absorption and the discovery of different compounds that amend cholesterol absorption, there is a series of cholesterol lowering drugs, which may decrease the level of serum cholesterol by altering its absorption. It is recognized that the effects of cholesterol lowering drugs as well as genetics of a person, loss of body weight, enzymes and proteins may increase the cholesterol altering effect, but the impact of these agents on the mechanism of cholesterol homeostasis are poorly understood. The disturbance of cholesterol homeostasis is also related with vascular changes associated with cardiac and kidney problems. Besides using different drugs and other means (plant sterol, enzyme, protein etc.), there is a need to improve the dietary pattern and life style. These may help to improve the cholesterol homeostasis.

show abstract

Up-regulation of Cholesterol Absorption Is a Mechanism for Cholecystokinin-induced Hypercholesterolemia

Cited by 15 publications

References 42 publications

Melatonin‐mediated inhibition of Purkinje neuron P‐type Ca²⁺ channels in vitro induces neuronal hyperexcitability through the phosphatidylinositol 3‐kinase‐dependent protein kinase C delta pathway

Melatonin‐mediated inhibition of Purkinje neuron P‐type Ca²⁺ channels in vitro induces neuronal hyperexcitability through the phosphatidylinositol 3‐kinase‐dependent protein kinase C delta pathway

Vitamin E intestinal absorption: Regulation of membrane transport across the enterocyte

Association between Cholesterol Homeostasis with Intestinal Proteins, Enzymes and Drugs in Absorption of Cholesterol and its Relationship with Vascular Diseases: A Review

Contact Info

Product

Resources

About

Up-regulation of Cholesterol Absorption Is a Mechanism for Cholecystokinin-induced Hypercholesterolemia

Cited by 15 publications

References 42 publications

Melatonin‐mediated inhibition of Purkinje neuron P‐type Ca2+ channels in vitro induces neuronal hyperexcitability through the phosphatidylinositol 3‐kinase‐dependent protein kinase C delta pathway

Melatonin‐mediated inhibition of Purkinje neuron P‐type Ca2+ channels in vitro induces neuronal hyperexcitability through the phosphatidylinositol 3‐kinase‐dependent protein kinase C delta pathway

Vitamin E intestinal absorption: Regulation of membrane transport across the enterocyte

Association between Cholesterol Homeostasis with Intestinal Proteins, Enzymes and Drugs in Absorption of Cholesterol and its Relationship with Vascular Diseases: A Review

Contact Info

Product

Resources

About

Melatonin‐mediated inhibition of Purkinje neuron P‐type Ca²⁺ channels in vitro induces neuronal hyperexcitability through the phosphatidylinositol 3‐kinase‐dependent protein kinase C delta pathway

Melatonin‐mediated inhibition of Purkinje neuron P‐type Ca²⁺ channels in vitro induces neuronal hyperexcitability through the phosphatidylinositol 3‐kinase‐dependent protein kinase C delta pathway