Document Detail

The Decline of Autophagy Contributes to Proximal Tubular Dysfunction During Sepsis.
MedLine Citation:
PMID:  22089196     Owner:  NLM     Status:  Publisher    
ABSTRACT: Severe sepsis associated with overproduction of TNF-α and ROS leads to energy depletion andcellular damage. Both ROS and damaged organelles induce autophagy for recycling nutrients tocombat pathological stress. To study whether autophagy plays a beneficial role in the pathogenesis ofrenal failure during sepsis, rats were subjected to cecal ligation and puncture (CLP) or shamoperation. Temporal relationship of autophagy and renal dysfunction were examined in vivo. Theresult showed that level of lipidated microtubule-associated protein light chain 3 (LC3-II), a markerof autophagy, elevated transiently at 3 h but declined at 9 h till 18 h after CLP. LC3 aggregation inrenal tissue showed a similar trend to the change of LC3-II protein. High levels of BUN andcreatinine as well as low tubular sodium reabsorption occurred at 18 h after CLP. The distribution ofautophagy located primarily in ACE (angiotensin converting enzyme, which is concentrated inproximal tubule) positive, but Calbindin D28k (Calcium-binding protein D28K; a marker of distaltubule) negative cells in renal cortex. Therefore, NRK-52E (proximal tubule epithelial cell line) cellswere used to further examine cell viability and DNA fragmentation after silencing or inducingautophagy. We found that knockdown of Atg7 (autophagy-related gene 7) exaggerates, while preincubationof rapamycin (an autophagy inducer) diminishes TNFα-induced cell death. These resultssuggest that the decline of sepsis-induced autophagy contributes to the proximal tubular dysfunctionand maintenance of sufficient autophagy prevents cell death. These data open prospects for therapies that activate autophagy during sepsis.
Hsiu-Wen Hsiao; Ke-Li Tsai; Li-Fang Wang; Yen-Hsu Chen; Pei-Chi Chiang; Shu-Mien Chuang; Chin Hsu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-15
Journal Detail:
Title:  Shock (Augusta, Ga.)     Volume:  -     ISSN:  1540-0514     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9421564     Medline TA:  Shock     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
1Department of Physiology, Faculty of Medicine, 3Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 4Graduate Institute of Medicine, College of Medicine; 2Department of Medicinal and Applied Chemistry, College of Life Science, Kaohsiung Medical University, Kaohsiung, 807 Taiwan.
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