Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


Thesis MS 2020 - Sandhya.pdf (1.86 MB)

ETD Abstract Container

Abstract Header

Apoptosis and necrosis drive muscle fiber loss in lipin1 deficient skeletal muscle

Sattiraju, Sandhya Ramani
http://rave.ohiolink.edu/etdc/view?acc_num=wright1598626794423032

Abstract Details

2020, Master of Science (MS), Wright State University, Biochemistry and Molecular Biology.
Mutations in lipin1 are suggested to be a common cause of massive rhabdomyolysis episodes in children, however, the molecular mechanism involved in the regulation of myofiber death by lipin1 is not known. In this study, we utilized the skeletal muscle from cell-type-specific lipin1 knockout (Lipin1Myf5cKO) mice to define cell death pathways involved in lipin1 deficient muscles. We observed a significant increase in centrally nucleated fibers and embryonic myosin heavy chain (EMyHC)-positive regenerating fibers in Lipin1Myf5cKO mice compared to wild-type (WT) mice, indicating an increased cycle of degeneration and regeneration in lipin1 deficient muscles. Lipin1 deficient muscles had significantly elevated pro-apoptotic factors (Bax, Bak, and cleaved caspase 9) and necroptotic proteins such as RIPK1, RIPK3, and MLKL compared with WT mice. Moreover, loss of membrane integrity is considered as a hallmark of cell death and we found that Lipin1Myf5cKO mice had significantly higher membrane disruptions as evidenced by increased IgG staining and elevated uptake of Evans Blue Dye (EBD) in muscle fibers. EBD-positive fibers were strongly colocalized with apoptotic or necrotic myofibers, suggesting an association between compromised plasma membrane integrity and cell death pathways. We further show that the absence of lipin1 leads to a significant decrease in the absolute and specific muscle force (normalized to muscle mass). Our work indicates that apoptosis and necroptosis are associated with a loss of membrane integrity in muscle lacking lipin1 and myofiber death may induce an expected decrease in contractile force and a defect in muscle function.
Hongmei Ren, Ph.D. (Advisor)
Weiwen Long, Ph.D. (Committee Member)
Michael Markey, Ph.D. (Committee Member)
58 p.
Biochemistry; Molecular Biology
lipin1; apoptosis; necrosis; membrane integrity; skeletal muscle

Recommended Citations

Citations

  • Sattiraju, S. R. (2020). Apoptosis and necrosis drive muscle fiber loss in lipin1 deficient skeletal muscle [Master's thesis, Wright State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=wright1598626794423032

    APA Style (7th edition)

  • Sattiraju, Sandhya Ramani. Apoptosis and necrosis drive muscle fiber loss in lipin1 deficient skeletal muscle. 2020. Wright State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=wright1598626794423032.

    MLA Style (8th edition)

  • Sattiraju, Sandhya Ramani. "Apoptosis and necrosis drive muscle fiber loss in lipin1 deficient skeletal muscle." Master's thesis, Wright State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=wright1598626794423032

    Chicago Manual of Style (17th edition)

wright1598626794423032
275
© 2020, all rights reserved.
This open access ETD is published by Wright State University and OhioLINK.