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Acid ceramidase ASAH1 is a key regulator of epidermal ceramide levels and composition.

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Title: Acid ceramidase ASAH1 is a key regulator of epidermal ceramide levels and composition.
Authors: Nobumoto, Wakana1, Naganuma, Tatsuro1, Nozaka, Nana1, Ohno, Yusuke1, Nojiri, Koki1, Kihara, Akio1 kihara@pharm.hokudai.ac.jp
Source: Journal of Biological Chemistry. Mar2026, Vol. 302 Issue 3, p1-14. 14p.
Subjects: Ceramides, Enzymes, Lipid metabolism, Keratinization, Skin permeability, Keratinocytes
Abstract: Maintenance of appropriate ceramide levels and composition in the stratum corneum of the epidermis is essential for skin barrier function. Although ceramide homeostasis is regulated by both synthesis and degradation, the extent of ceramide degradation in the epidermis, as well as the ceramidase responsible for this degradation, has thus far remained unclear. Here, we found that the acid ceramidase ASAH1 is strongly expressed in differentiated human keratinocytes. To investigate its role, we generated ASAH1 KO cells using immortalized human keratinocytes and analyzed their ceramide levels. Under differentiation conditions, ASAH1 KO keratinocytes exhibited a marked accumulation of ceramide classes composed of sphingosine (S) or dihydrosphingosine (dS) and nonhydroxy fatty acid (N) (ceramides NS and NdS). In contrast, ceramides with (an) additional hydroxyl group(s)—such as those containing phytosphingosine (P) or 6-hydroxysphingosine (H) and N or α-hydroxy fatty acid (A) (ceramides NP, NH, AP, and AH)—showed a moderate or no increase. Similar results were obtained upon treatment with SABRAC, a specific ASAH1 inhibitor. In vitro enzyme assays revealed that ASAH1 exhibited strong activity toward NS and NdS, weak activity toward NP and NH, and no activity toward AP. These results indicate that ASAH1-mediated ceramide class-dependent degradation occurs in differentiated human keratinocytes. This degradation likely plays an important role in maintaining appropriate ceramide levels and class composition in the stratum corneum, thereby contributing to the integrity of the skin barrier. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
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Header DbId: egs
DbLabel: Engineering Source
An: 192571779
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
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  Data: Acid ceramidase ASAH1 is a key regulator of epidermal ceramide levels and composition.
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  Data: <searchLink fieldCode="AR" term="%22Nobumoto%2C+Wakana%22">Nobumoto, Wakana</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Naganuma%2C+Tatsuro%22">Naganuma, Tatsuro</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Nozaka%2C+Nana%22">Nozaka, Nana</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Ohno%2C+Yusuke%22">Ohno, Yusuke</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Nojiri%2C+Koki%22">Nojiri, Koki</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Kihara%2C+Akio%22">Kihara, Akio</searchLink><relatesTo>1</relatesTo><i> kihara@pharm.hokudai.ac.jp</i>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Biological+Chemistry%22">Journal of Biological Chemistry</searchLink>. Mar2026, Vol. 302 Issue 3, p1-14. 14p.
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  Data: <searchLink fieldCode="DE" term="%22Ceramides%22">Ceramides</searchLink><br /><searchLink fieldCode="DE" term="%22Enzymes%22">Enzymes</searchLink><br /><searchLink fieldCode="DE" term="%22Lipid+metabolism%22">Lipid metabolism</searchLink><br /><searchLink fieldCode="DE" term="%22Keratinization%22">Keratinization</searchLink><br /><searchLink fieldCode="DE" term="%22Skin+permeability%22">Skin permeability</searchLink><br /><searchLink fieldCode="DE" term="%22Keratinocytes%22">Keratinocytes</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Maintenance of appropriate ceramide levels and composition in the stratum corneum of the epidermis is essential for skin barrier function. Although ceramide homeostasis is regulated by both synthesis and degradation, the extent of ceramide degradation in the epidermis, as well as the ceramidase responsible for this degradation, has thus far remained unclear. Here, we found that the acid ceramidase ASAH1 is strongly expressed in differentiated human keratinocytes. To investigate its role, we generated ASAH1 KO cells using immortalized human keratinocytes and analyzed their ceramide levels. Under differentiation conditions, ASAH1 KO keratinocytes exhibited a marked accumulation of ceramide classes composed of sphingosine (S) or dihydrosphingosine (dS) and nonhydroxy fatty acid (N) (ceramides NS and NdS). In contrast, ceramides with (an) additional hydroxyl group(s)—such as those containing phytosphingosine (P) or 6-hydroxysphingosine (H) and N or α-hydroxy fatty acid (A) (ceramides NP, NH, AP, and AH)—showed a moderate or no increase. Similar results were obtained upon treatment with SABRAC, a specific ASAH1 inhibitor. In vitro enzyme assays revealed that ASAH1 exhibited strong activity toward NS and NdS, weak activity toward NP and NH, and no activity toward AP. These results indicate that ASAH1-mediated ceramide class-dependent degradation occurs in differentiated human keratinocytes. This degradation likely plays an important role in maintaining appropriate ceramide levels and class composition in the stratum corneum, thereby contributing to the integrity of the skin barrier. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – Type: doi
        Value: 10.1016/j.jbc.2026.111178
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      – Code: eng
        Text: English
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        PageCount: 14
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      – SubjectFull: Ceramides
        Type: general
      – SubjectFull: Enzymes
        Type: general
      – SubjectFull: Lipid metabolism
        Type: general
      – SubjectFull: Keratinization
        Type: general
      – SubjectFull: Skin permeability
        Type: general
      – SubjectFull: Keratinocytes
        Type: general
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      – TitleFull: Acid ceramidase ASAH1 is a key regulator of epidermal ceramide levels and composition.
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            NameFull: Naganuma, Tatsuro
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              Text: Mar2026
              Type: published
              Y: 2026
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