Alcohol induces α2‐6sialo mucin O‐glycans that kill U937 macrophages mediated by sialic acid‐binding immunoglobulin‐like lectin 7 (Siglec 7)
Alcohol misuse increases infections and cancer fatalities, but mechanisms underlying its toxicity are ill‐defined. We show that alcohol treatment of human tracheobronchial epithelial cells leads to inactivation of giantin‐mediated Golgi targeting of glycosylation enzymes. Loss of core 2 N‐acetylgluc...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-01-01
|
| Series: | FEBS Open Bio |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/2211-5463.13919 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841557037475954688 |
|---|---|
| author | Pi‐Wan Cheng Vishwanath‐Reddy Hothpet Ganapati Bhat Kristina Bailey Lei Li Derrick R. Samuelson |
| author_facet | Pi‐Wan Cheng Vishwanath‐Reddy Hothpet Ganapati Bhat Kristina Bailey Lei Li Derrick R. Samuelson |
| author_sort | Pi‐Wan Cheng |
| collection | DOAJ |
| description | Alcohol misuse increases infections and cancer fatalities, but mechanisms underlying its toxicity are ill‐defined. We show that alcohol treatment of human tracheobronchial epithelial cells leads to inactivation of giantin‐mediated Golgi targeting of glycosylation enzymes. Loss of core 2 N‐acetylglucosaminyltransferase 1, which uses only giantin for Golgi targeting, coupled with shifted targeting of other glycosylation enzymes to Golgi matrix protein 130‐Golgi reassembly stacking protein 65, the site normally used by core 1 enzyme, results in loss of sialyl Lewis x and increase of sialyl Lewis a and α2‐6sialo mucin O‐glycans. The α2‐6sialo mucin O‐glycans induced by alcohol cause death of U937 macrophages mediated by sialic acid‐binding immunoglobulin‐like lectin 7. These results provide a mechanistic insight into the cause of the toxic effects of alcohol and might contribute to the development of therapies to alleviate its toxicity. |
| format | Article |
| id | doaj-art-b52e9ec3cdd8419283da82c6811f33fe |
| institution | Kabale University |
| issn | 2211-5463 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj-art-b52e9ec3cdd8419283da82c6811f33fe2025-01-07T02:27:34ZengWileyFEBS Open Bio2211-54632025-01-0115116517910.1002/2211-5463.13919Alcohol induces α2‐6sialo mucin O‐glycans that kill U937 macrophages mediated by sialic acid‐binding immunoglobulin‐like lectin 7 (Siglec 7)Pi‐Wan Cheng0Vishwanath‐Reddy Hothpet1Ganapati Bhat2Kristina Bailey3Lei Li4Derrick R. Samuelson5Department of Biochemistry and Molecular Biology, College of Medicine University of Nebraska Medical Center Omaha NE USADepartment of Biochemistry and Molecular Biology, College of Medicine University of Nebraska Medical Center Omaha NE USADepartment of Biochemistry and Molecular Biology, College of Medicine University of Nebraska Medical Center Omaha NE USADepartment of Internal Medicine, College of Medicine University of Nebraska Medical Center Omaha NE USADepartment of Chemistry and Center for Diagnostic & Therapeutics Georgia State University Atlanta GA USADepartment of Internal Medicine, College of Medicine University of Nebraska Medical Center Omaha NE USAAlcohol misuse increases infections and cancer fatalities, but mechanisms underlying its toxicity are ill‐defined. We show that alcohol treatment of human tracheobronchial epithelial cells leads to inactivation of giantin‐mediated Golgi targeting of glycosylation enzymes. Loss of core 2 N‐acetylglucosaminyltransferase 1, which uses only giantin for Golgi targeting, coupled with shifted targeting of other glycosylation enzymes to Golgi matrix protein 130‐Golgi reassembly stacking protein 65, the site normally used by core 1 enzyme, results in loss of sialyl Lewis x and increase of sialyl Lewis a and α2‐6sialo mucin O‐glycans. The α2‐6sialo mucin O‐glycans induced by alcohol cause death of U937 macrophages mediated by sialic acid‐binding immunoglobulin‐like lectin 7. These results provide a mechanistic insight into the cause of the toxic effects of alcohol and might contribute to the development of therapies to alleviate its toxicity.https://doi.org/10.1002/2211-5463.13919ethanolgiantinSiglec 7U937 macrophagesα2‐6sialo mucin O‐glycans |
| spellingShingle | Pi‐Wan Cheng Vishwanath‐Reddy Hothpet Ganapati Bhat Kristina Bailey Lei Li Derrick R. Samuelson Alcohol induces α2‐6sialo mucin O‐glycans that kill U937 macrophages mediated by sialic acid‐binding immunoglobulin‐like lectin 7 (Siglec 7) FEBS Open Bio ethanol giantin Siglec 7 U937 macrophages α2‐6sialo mucin O‐glycans |
| title | Alcohol induces α2‐6sialo mucin O‐glycans that kill U937 macrophages mediated by sialic acid‐binding immunoglobulin‐like lectin 7 (Siglec 7) |
| title_full | Alcohol induces α2‐6sialo mucin O‐glycans that kill U937 macrophages mediated by sialic acid‐binding immunoglobulin‐like lectin 7 (Siglec 7) |
| title_fullStr | Alcohol induces α2‐6sialo mucin O‐glycans that kill U937 macrophages mediated by sialic acid‐binding immunoglobulin‐like lectin 7 (Siglec 7) |
| title_full_unstemmed | Alcohol induces α2‐6sialo mucin O‐glycans that kill U937 macrophages mediated by sialic acid‐binding immunoglobulin‐like lectin 7 (Siglec 7) |
| title_short | Alcohol induces α2‐6sialo mucin O‐glycans that kill U937 macrophages mediated by sialic acid‐binding immunoglobulin‐like lectin 7 (Siglec 7) |
| title_sort | alcohol induces α2 6sialo mucin o glycans that kill u937 macrophages mediated by sialic acid binding immunoglobulin like lectin 7 siglec 7 |
| topic | ethanol giantin Siglec 7 U937 macrophages α2‐6sialo mucin O‐glycans |
| url | https://doi.org/10.1002/2211-5463.13919 |
| work_keys_str_mv | AT piwancheng alcoholinducesa26sialomucinoglycansthatkillu937macrophagesmediatedbysialicacidbindingimmunoglobulinlikelectin7siglec7 AT vishwanathreddyhothpet alcoholinducesa26sialomucinoglycansthatkillu937macrophagesmediatedbysialicacidbindingimmunoglobulinlikelectin7siglec7 AT ganapatibhat alcoholinducesa26sialomucinoglycansthatkillu937macrophagesmediatedbysialicacidbindingimmunoglobulinlikelectin7siglec7 AT kristinabailey alcoholinducesa26sialomucinoglycansthatkillu937macrophagesmediatedbysialicacidbindingimmunoglobulinlikelectin7siglec7 AT leili alcoholinducesa26sialomucinoglycansthatkillu937macrophagesmediatedbysialicacidbindingimmunoglobulinlikelectin7siglec7 AT derrickrsamuelson alcoholinducesa26sialomucinoglycansthatkillu937macrophagesmediatedbysialicacidbindingimmunoglobulinlikelectin7siglec7 |