● 아폽토시스
세라마이드의 가장 많이 연구된 역할 중 하나는 세포자멸사 입니다.
Apoptosis(프로그램된 세포 사멸)는
정상적인 세포 항상성의 유지에 필수적이며
다양한 형태의 세포 스트레스에 대한
생리학적 반응입니다.
세라마이드 축적은 이온화 방사선, [2] [12]
UV 광선, [13] , TNF-알파 , [14] 및 화학요법제를
포함하는 다수의 세포사멸 약제로 세포를 처리한 후 발견되었습니다.
이것은 이러한 모든 약제의 생물학적 반응에서 세라마이드의 역할을 시사합니다.
암세포에서 세포자멸사를 유도하는 효과 때문에 세라마이드는 "종양 억제 지질"로 불립니다.
여러 연구에서 세포 사멸 사건에서
세라마이드의 특정 역할을 추가로 정의하려고 시도했으며 일부 증거는 세포자멸사를 유도하는 미토콘드리아 상류의 세라마이드 기능을 시사 합니다.
그러나 세포 사멸에서 세라마이드의 역할에 대한 연구의 상충되고 다양한 특성으로 인해
이 지질이 세포 사멸을 조절하는 메커니즘은
여전히 애매합니다. [15]
As a bioactive lipid, ceramide has been implicated in a variety of physiological functions including
apoptosis,
cell growth arrest,
differentiation,
cell senescence,
cell migration and adhesion.[3]
Roles for ceramide and its downstream metabolites have also been suggested in a number of pathological states including cancer, neurodegeneration,
diabetes, microbial pathogenesis,
obesity, and inflammation.[5][6]
Ceramides induce skeletal muscle
insulin resistance
when synthesized as a result of saturated fat activation of TLR4 receptors.[7]
Unsaturated fat does not have this effect.[7]
Ceramides induce insulin resistance
in many tissues by inhibition of Akt/PKB signaling.[8]
Aggregation of LDL cholesterol
by ceramide causes LDL retention in arterial walls, leading
to atherosclerosis.[9]
Ceramides cause endothelial dysfunction by activating protein phosphatase 2 (PP2A).[10]
In mitochondria, ceramide suppresses the electron transport chain and induces production of reactive oxygen species.[11]
1) Apoptosis
One of the most studied roles of ceramide pertains to its function as a proapoptotic molecule.
Apoptosis, or Type I programmed cell death, is essential for the maintenance of normal cellular homeostasis
and is an important physiological response to many forms of cellular stress.
Ceramide accumulation has been found following treatment of cells with a number of apoptotic agents including ionizing radiation,[2][12]
UV light,[13] TNFalpha,[14]
and chemotherapeutic agents.
This suggests a role for ceramide
in the biological responses of all these agents. Because of its apoptosis-inducing effects in cancer cells, ceramide has been termed the
"tumor suppressor lipid".
Several studies have attempted to define further the specific role of ceramide
in the events of cell death and some evidence suggests ceramide functions upstream of the mitochondria
in inducing apoptosis.
However, owing to the conflicting and variable nature of studies into the role of ceramide in apoptosis, the mechanism by which this lipid regulates apoptosis remains elusive.[15]
2) Skin
Ceramide is the main component of the stratum corneum of the epidermis layer of human skin.[16][17]
Together with cholesterol and saturated fatty acids, ceramide creates a water-impermeable, protective organ to prevent excessive water loss due to evaporation as well as a barrier against the entry of microorganisms.[17]
In the hyperplastic disorder psoriasis
the water permeability barrier is compromised.[18]
Ceramide VI is the most abundant ceramide of the skin, along with ceramide II, and has been exploited to model the organization of the stratum corneum lipidic network.[19][20]
The stratum corneum is composed of 50% ceramides, 25% cholesterol, and 15% free fatty acids.[18]
Key components of the extracellular lipid lamellae of the stratum corneum are
ultra long chain
(C28-C36)ceramides.[21]
※ 지방산 탄소수
단쇄지방산 4개
중쇄지방산 6개-10개
장쇄지방산 12-20개
초장쇄지방산 22-36개
With aging there is a decline in
ceramide and cholesterol in the stratum corneum of humans.[22]
A clinical trial using ceramide-rich wheat extract showed increased skin hydration in those taking the extract rather than the placebo.[23]
3) Hormonal
Inhibition of ceramide synthesis with myriocin in obese mice
may lead to both improved leptin signaling
and decreased insulin resistance
by decreasing SOCS-3 expression.[24]
An elevated level of ceramide
can cause insulin resistance by inhibiting the ability of insulin to activate the insulin signal
transduction pathway and/or via the activation of JNK.[25]
(참조) https://en.m.wikipedia.org/wiki/Ceramide
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#스핑고신
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