Course Meeting Times
Lectures: 1 session / week, 2 hours / session
7.05 General Biochemistry
7.06 Cell Biology
7.28 Molecular Biology
The emergence of oxygen was responsible for the origin of much of life as we know it, coinciding with the evolution of eukaryotic and multicellular organisms. However, environmental oxygen was highly toxic to almost an entire subset of species, namely the anaerobes, making oxygen arguably the most fatal pollutant in the existence of the Earth. To deal with the damaging effects of oxygen radicals generated during mitochondrial respiration, aerobic organisms have had to develop protective mechanisms, such as antioxidant enzymes, redox regulatory proteins and repair pathways. At controlled levels, reactive oxygen species (ROS) perform important biological functions, for example acting as signal transducers in mitogenic pathways and in mediating the immune inflammatory response. However, excessive levels of oxygen radicals have been implicated in a wide array of human diseases, ranging from premature aging to cancer. In this course, we will discuss the physiological consequences of oxidative stress and altered ROS levels, with emphasis on understanding the complex dual role of ROS as both cellular signaling molecules and cellular damaging agents. To understand how we are protected from the intrinsic reactivity of oxygen, we will start with a survey of basic oxygen radical biochemistry followed by a discussion of the mechanisms of action of cellular as well as dietary antioxidants. After considering the normal physiological roles of oxidants, we will examine the effects of elevated ROS and a failure of cellular redox capacity on the rate of organismal and cellular aging as well as on the onset and progression of several major diseases that are often age-related. Topics will include ROS-induced effects on stem cell regeneration, insulin resistance, heart disease, neurodegenerative disorders and cancer. The role of antioxidants in potential therapeutic strategies for modulating ROS levels will also be discussed.
Course Format and Objectives
This course consists of 12 classes and will involve the discussion of two papers from the primary literature per session with the emphasis on class discussion. No lectures will be given. You will find that the role of ROS in different pathologies is often a source of lively debate within the scientific community, and frequently the assigned reading will be chosen to reflect this fact. Active class participation is both encouraged and expected. The papers must be read in detail in advance of each session. A brief introduction will be given to the topics and papers to be discussed during the end of the previous session. Students will lead the discussions for the papers that deal with the pathologies of oxidative stress.
This course is designed to give you insight into the complex role of oxygen radicals in normal cell physiology and in causing the cellular damage implicated in a number of diseases. The assigned literature is intended to familiarize you with the scientific approaches used and to provide you with a general overview of the field.
Oxidative glucose metabolism substrates (a.k.a. cookies) and antioxidants (fruits and chocolate) will be regularly provided.
- You are expected to have a basic background in general chemistry and in cell and molecular biology.
- Attendance is important for every session. If you cannot attend, please let me know well in advance. Depending on my schedule and that of the other students, we may be able to reschedule to ensure full attendance.
- You will be expected to complete all the assigned reading before each class.
- Presentations and papers must be completed by the due dates. Extensions will be granted only under extremely extenuating circumstances and only if you inform me well in advance.
This course is graded pass/fail, and the grade depends on attendance, participation, and the successful completion of two assignments.
||Introduction and background
||The high price of energy: Mitrochondrial production of ROS
||Radical messengers: ROS as facilitators of cellular signaling
||Hired assassins: ROS in anti-pathogen defense
||Antioxidants: fighting the good fight
||The free radical theory: ROS and aging
||First paper due
||The root of the problem: oxidative damage in stem cell renewal
||Topics for final paper due
||Balancing act: ROS effects on insulin resistance and diabetes
||Breaking hearts: ROS in ischemic reperfusion injury
||Brain drain: oxidative stress in neurodegenerative diseases
||Introduction paragraph of final paper due
||Foot-soldiers of renegade cells: ROS in cancer and oncogenic transformation
||Fighting fire with fire: more ROS or less ROS as therapeutic strategies?
||Final paper due
||Final class presentations