Acid and neutral sphingomyelinase, ceramide synthase, and acid ceramidase activities in cutaneous aging

Acid and neutral sphingomyelinase, ceramide synthase, and acid ceramidase activities in cutaneous aging
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DOI:
10.1111/j.0906-6705.2005.00342.x
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发表时间:
2005-08-01
影响因子:
3.6
通讯作者:
Schütze, S
Schütze, S
中科院分区:
医学2区
文献类型:
--
作者:
Jensen, JM;Förl, M;Schütze, S

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在老化的皮肤中,已经描述了角质层神经酰胺的水平降低。表皮神经酰胺通过鞘磷脂水解或由鞘氨醇和脂肪酸合成而产生,并被神经酰胺酶降解。我们最近发现,表皮酸性鞘磷脂酶(A-SMase)产生的神经酰胺与角质层脂质双层,提供了皮肤的渗透屏障功能的结构功能。在这里,我们研究了活动的表皮A-SMase,神经酰胺合成酶,神经酰胺酶在按时间顺序老化与年轻的无毛小鼠皮肤。我们发现减少A-SMase和神经酰胺合成酶的活动在老年小鼠的表皮。然而,对酶定位的研究显示,外表皮中的A-SMase活性保持不变,持续高水平,这与基础条件下在老化皮肤中发现的正常屏障功能相关。内表皮A-SMase和神经酰胺合酶活性降低,与衰老中渗透屏障修复能力降低相关。神经酰胺酶活性不具有年龄依赖性。总之,我们发现在老化皮肤的内表皮中产生神经酰胺的SMase和神经酰胺合成酶的活性降低,解释了其在屏障修复中的能力降低。相比之下,A-SMase活性在外表皮是不变的,表明这种酶是至关重要的基础渗透屏障稳态参与。
In aged skin, decreased levels of stratum corneum ceramides have been described. Epidermal ceramides are generated by sphingomyelin hydrolysis or synthesis from sphingosin and fatty acids and are degraded by ceramidase. We recently showed that epidermal acid sphingomyelinase (A-SMase) generates ceramides with structural function in the stratum corneum lipid bilayers, which provide for the permeability barrier function of the skin. Here, we examined the activities of epidermal A-SMase, ceramide synthase, and ceramidase in chronologically aged versus young hairless mouse skin. We found reduced A-SMase and ceramide synthase activities in the epidermis of aged mice. However, studies on enzyme localization revealed unchanged, ongoing high A-SMase activity in the outer epidermis, which correlated with reported normal barrier function found in aged skin under basal conditions. Reduced A-SMase and ceramide synthase activity was noted in the inner epidermis, correlating with reduced capacity for permeability barrier repair in aging. Ceramidase activity was not age dependent. In summary, we found reduced activities of ceramide-generating SMase and ceramide synthase in the inner epidermis of aged skin, explaining its reduced capacity in barrier repair. In contrast, A-SMase activity in the outer epidermis was unchanged, indicating that this enzyme is crucially involved in basal permeability barrier homeostasis.