Exploring pathways of NO and H2S signaling in metabolic depression: The case of anoxic turtles

Abstract

In contrast to most vertebrates, freshwater turtles of the genera Trachemys and Chrysemys survive oxygen deprivation for long periods of time. This remarkable tolerance makes them ideal August Krogh's model animals to study adaptions to survive oxygen deprivation. The gasotransmitters nitric oxide (NO) and hydrogen sulfide (H2S) and their metabolic derivatives are central in regulating the physiological responses to oxygen deprivation. Here, we explore the role of these signaling molecules in the anoxia tolerance of the freshwater turtle, including metabolic suppression and protection against oxidative damage with oxygen deprivation. We describe the interaction of NO and H2S with protein thiols and specifically how this regulates the function of central metabolic enzymes. These interactions contribute both to metabolic suppression and to prevent oxidative damage with oxygen deprivation. Furthermore, NO and H2S interact with ferrous and ferric heme iron, respectively, which affects the activity of central heme proteins. In turtles, these interactions contribute to regulate oxygen consumption in the mitochondria, as well as vascular tone and blood flow during oxygen deprivation. The versatile biological effects of NO and H2S underscores the importance of these volatile signaling molecules in the remarkable tolerance of freshwater turtles to oxygen deprivation.

New insights into survival strategies to oxygen deprivation in anoxia‐tolerant vertebrates

“…Hypoxic goldfish also shows downregulation of complex IV in several organs but not in the heart, 40 probably reflecting that cardiac output is maintained in anoxia, as seen in crucian carp. 6 A factor that may inhibit complex IV activity in vivo is the gaseous signaling molecule NO, 53 , 54 which has been detected (as heme‐bound NO) at particularly high levels in tissues from anoxic crucian carp 55 and turtle. 56 , 57 Specific sample treatments are essential for stabilizing NO in tissues, which might explain why sometimes NO inhibition is lost.…”

Cytoskeletal Arrest: An Anoxia Tolerance Mechanism

“…The membrane-permeable [ 205 ] gasotransmitters hydrogen sulphide (H 2 S), nitric oxide (NO), and carbon monoxide (CO) are of increasing interest in anoxia tolerance (reviewed in [ 206 ]), and all three have documented regulatory effects on MMP, ROS production, and cytoskeletal dynamics in mammals. Therefore, their functions, as well as their levels in overwintering animals and anoxic turtles, warrant consideration.…”

“…Only H 2 S and NO have been investigated in turtles (reviewed in [ 206 ]). Free H 2 S decreases with cold acclimation in red-eared turtle liver and bound H 2 S increases with cold acclimation in turtle brain.…”