NF-κB mediates the protein loss induced by TNF-α in differentiated skeletal muscle myotubes

American Journal of Physiology - Regulatory Integrative and Comparative Physiology - Tập 279 Số 4 - Trang R1165-R1170 - 2000
Yiping Li1, Micheal B. Reid2
1Department of Medicine, Baylor College of Medicine, Houston, Texas 77030 USA
2Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.

Tóm tắt

Nuclear factor-κB (NF-κB) regulates the transcription of a variety of genes involved in immune responses, cell growth, and cell death. However, the role of NF-κB in muscle biology is poorly understood. We recently reported that tumor necrosis factor-α (TNF-α) rapidly activates NF-κB in differentiated skeletal muscle myotubes and that TNF-α acts directly on the muscle cell to induce protein degradation. In the present study, we ask whether NF-κB mediates the protein loss induced by TNF-α. We addressed this problem by creating stable, transdominant negative muscle cell lines. C2C12 myoblasts were transfected with viral plasmid constructs that induce overexpression of mutant I-κBα proteins that are insensitive to degradation via the ubiquitin-proteasome pathway. These mutant proteins selectively inhibit NF-κB activation. We found that differentiated myotubes transfected with the empty viral vector (controls) underwent a drop in total protein content and in fast-type myosin heavy-chain content during 72 h of exposure to TNF-α. In contrast, total protein and fast-type myosin heavy-chain levels were unaltered by TNF-α in the transdominant negative cell lines. TNF-α did not induce apoptosis in any cell line, as assessed by DNA ladder and annexin V assays. These data indicate that NF-κB is an essential mediator of TNF-α-induced catabolism in differentiated muscle cells.

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Tài liệu tham khảo

10.1093/nar/19.9.2499

10.1097/00001573-199905000-00004

10.1016/S0092-8674(00)81318-5

10.1016/0014-5793(94)80163-0

10.1128/MCB.15.5.2809

10.1002/j.1460-2075.1996.tb00524.x

10.1016/S0899-9007(98)00108-7

10.1101/gad.9.13.1586

10.1016/0960-7404(94)90027-2

10.1016/S0733-8619(05)70188-2

10.1016/0014-5793(93)81341-V

10.1006/bbrc.1995.2848

10.1007/BF00926829

10.1128/MCB.19.8.5785

10.1016/S0764-4469(99)80033-X

10.1016/S0092-8674(00)80984-8

Johansson AS, 1998, Lakartidningen, 95, 44

Karin M., 1998, Cancer J Sci Am, 4, S92

10.1089/ars.1999.1.1-97

10.1096/fasebj.12.10.871

10.1016/S0092-8674(00)81375-6

10.1006/bbrc.1996.5827

10.1016/S0303-7207(98)00105-1

Nakashima J, 1995, Cancer Res, 55, 4881

10.1016/0092-8674(87)90028-6

10.1080/14017439950141407

10.3109/10408369309084669

10.1006/bbrc.1997.7206

10.1080/07315724.1996.10718583

10.1093/jn/129.1.243S

10.1084/jem.167.3.1211

10.1111/j.1365-2362.1992.tb01495.x

Weinroth SE, 1995, Infect Agents Dis, 4, 76

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American Journal of Physiology - Regulatory Integrative and Comparative Physiology

Tập 279 Số 4

R1165-R1170

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