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Molecular Roles of ROS in Mouse Respiratory Skeletal Muscle

ZHOU, TINGYANG, ZHOU
http://rave.ohiolink.edu/etdc/view?acc_num=osu1531848449464785

Abstract Details

2018, Doctor of Philosophy, Ohio State University, Biophysics.
Reactive oxygen species (ROS) can be induced in response to external stress such as hypoxia and ionizing radiation within the biological system. The current dissertation explored the positive and negative roles of ROS under these two stresses, respectively. In Chapter 2, I tested the hypothesis that both acute and chronic PO2 cycling can improve the diaphragmatic function during hypoxia. Acute PO2 cycling involves exposing the muscle to alternating low and high O2 levels for one, three, five, and ten cycles, respectively. In both healthy and chronic obstructive pulmonary disease mouse models, we found that diaphragm treated with five cycles of acute PO2 cycling showed increased fatigue resistance to hypoxia. However, the inhibition of ROS, phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), extracellular signal-regulated kinases (ERK), mitochondrial ATP sensitive K+ channels, or mitochondrial permeability transition pores (mPTP) closure using the respective inhibitors/mediators all abolished the protection conferred by acute PO2 cycling. The results suggest that the signaling cascades may be involved in mechanisms of acute PO2 cycling. On the other hand, chronic PO2 cycling was also performed on the whole animal model. The healthy and smoking mice were subjected to alternating 2 min of low and 2 min of normal O2 levels, repeated for five cycles a day. This protocol was performed for one, two, three or four weeks, respectively. Our results show that only two weeks of PO2 cycling substantially improved diaphragm muscle function during hypoxia. The mice treated with two-week PO2 cycling also demonstrated improved diaphragm vertical displacement and slower breathing rate, suggesting improved diaphragm function. The diaphragm capillary density and hemoglobin levels were also found to be elevated by two weeks of PO2 cycling training. Our results suggest that PO2 cycling treatment can effectively protect diaphragmatic function potentially through ROS-mediated cellular adaptive responses. In chapter 3, I evaluated the effects of off-target radiation on the redox and functionality of diaphragm muscle in a mouse model. Male C57BL6 mice received one-time ionizing radiation (IR) of 10 Gy on their diaphragmatic area. On the 1st, 3rd, 5th, and 7th days after IR, the muscle function and contraction-related extracellular ROS formation in the diaphragm was determined. The results show that the diaphragmatic function was compromised by IR on days 5 and 7, and there was a significant increase in ROS release from the contractile muscle in irradiated group during days 3-7 following IR. We then examined the effects of 10 Gy of IR on C2C12 myocytes. Following one-time 10 Gy of radiation on the cells, the oxidative stress and cell death was evaluated on the 1st, 3rd, 5th, and 7th days. The results show that ROS formation and cell death was significantly increased in irradiated group as compared to control on the 5th and 7th days. Our results suggest that 10 Gy of IR can cause negative impact on the diaphragmatic contractile function, which is potentially associated with increased oxidative stress and cell death. Protective strategies should be considered when radiation target is located close to the diaphragm.
Li Zuo, PhD (Advisor)
Jonathan Davis, PhD (Committee Member)
Hua Zhu, PhD (Committee Member)
190 p.
Biomedical Research; Physiology
PO2 cycling; hypoxia; preconditioning; radiation; stress; mice; chronic obstructive pulmonary diseases

Recommended Citations

Citations

  • ZHOU, ZHOU, T. (2018). Molecular Roles of ROS in Mouse Respiratory Skeletal Muscle [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1531848449464785

    APA Style (7th edition)

  • ZHOU, ZHOU, TINGYANG. Molecular Roles of ROS in Mouse Respiratory Skeletal Muscle . 2018. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1531848449464785.

    MLA Style (8th edition)

  • ZHOU, ZHOU, TINGYANG. "Molecular Roles of ROS in Mouse Respiratory Skeletal Muscle ." Doctoral dissertation, Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1531848449464785

    Chicago Manual of Style (17th edition)

osu1531848449464785
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This open access ETD is published by The Ohio State University and OhioLINK.