Exercise for Cardiovascular Disease Prevention and Treatment From Molecular to Clinical, Part 1

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6.2 Exercise Attenuates ROS Generation via Mitochondrial

Electron Leakage

In oxidative phosphorylation, the transfer of electrons into the electron transport

chain located on the inner mitochondrial membrane is directly related to the con-

centration of intracellular glucose. Under hyperglycemic conditions, the electron

transport chain become saturated and electrons are forced to be transferred to oxy-

gen and generates superoxide anions (O 2 •) [ 119 ] (Fig. 12.2).

Superoxide dismutase (SOD) catalyzes conversion of the generated O 2 • to hydro-

gen peroxide (H 2 O 2 ) which is then decomposed by glutathione peroxidase (GPx)

and catalase (CAT). H 2 O 2 decomposition can produce hydroxyl radicals (OH•)

which are highly damaging. OH• radicals induce the formation of the mitochondrial

permeability transition pore (MPTP). In oxidative stress conditions, H+ passes down

the electrochemical gradient through pores in the inner mitochondrial membrane

into the mitochondrial matrix without ATP generation. This uncoupling of the elec-

tron transport chain leads to further generation of O 2 •, swelling of the mitochondrial

matrix and leakage of cytochrome C into the cytosol causing apoptosis [ 120 ].

Experimental [ 26 , 27 , 111 ] and clinical studies [ 112 ] have reported excessive

mitochondrial ROS generation which contributes to mitochondrial dysfunction.

Mitochondrial ROS can damage membranes and DNA, and impair the activity of

electron transport chain, generating more ROS [ 121 ]. This notion was supported by

the findings of Shen et al. [ 122 ] who reported reduced ROS and normalized mito-

chondrial function via overexpression of the mitochondrial manganese SOD

(MnSOD) in the heart.

Regarding the effect of exercise on ROS-induced mitochondrial dysfunction, a

transient increase in cardiac ROS has been reported after acute bout of exercise

Fig. 12.1 Hyperglycemia-
induced superoxide (O 2 •)
generating pathways. ETC
electron transport chain,
MPTP mitochondrial
permeability transition
pore, NADPH nicotinamide
adenine dinucleotide
phosphate, AGEs advanced
glycation end-products,
eNOS endothelial nitric
oxide synthase, PKC
protein kinase C

A.M. Mahmoud