(2S)-2-Amino-8-nonenoic acid

Hydrogen sulfide (H2S) has been considered the third gaseous signaling molecule that plays important roles in a wide range of physiological and pathological conditions. However, there has been some controversy on the role of H2S in autophagy. Recent studies indicate that a number of signaling pathways are involved in the pro-autophagy effect of H2S, such as PI3K/Akt/mTOR, AMPK/mTOR, LKB1/STRAD/MO25, and miR-30c signaling pathways. On the other hand, there are many signaling pathways that play important roles in the anti-autophagy effect of H2S, including SR-A, PI3K/SGK1/GSK3β, PI3K/AKT/mTOR, Nrf2-ROS-AMPK, AMPK/mTOR, and JNK1 signaling pathways. Novel H2S-releasing donors/drugs could be designed and identified in order to increase the therapeutic effects by mediating autophagy in human diseases. In this review, the H2S metabolism in mammals is summarized and the effects of signaling pathways in H2S-mediated autophagy are further discussed.

Hydrogen sulfide (H2S) is a ubiquitous small gaseous signaling molecule, playing an important role in many physiological processes and joining nitric oxide and carbon monoxide in the group of signaling agents termed gasotransmitters. Endogenous concentrations of H2S are generally low, making it difficult to discern precise biological functions. As such, probing the physiological roles of H2S is aided by exogenous delivery of the gas in cell and animal studies. This need for an exogenous source of H2S provides a unique challenge for chemists to develop chemical tools that facilitate the study of H2S under biological conditions. Compounds that degrade in response to a specific trigger to release H2S, termed H2S donors, include a wide variety of functional groups and delivery systems, some of which mimic the tightly controlled endogenous production in response to specific, biologically relevant conditions. This review examines a variety of H2S donor systems classified by their H2S-releasing trigger as well as their H2S release profiles, byproducts, and potential therapeutic applications.

The important life-supporting role of hydrogen sulfide (H(2)S) has evolved from bacteria to plants, invertebrates, vertebrates, and finally to mammals. Over the centuries, however, H(2)S had only been known for its toxicity and environmental hazard. Physiological importance of H(2)S has been appreciated for about a decade. It started by the discovery of endogenous H(2)S production in mammalian cells and gained momentum by typifying this gasotransmitter with a variety of physiological functions. The H(2)S-catalyzing enzymes are differentially expressed in cardiovascular, neuronal, immune, renal, respiratory, gastrointestinal, reproductive, liver, and endocrine systems and affect the functions of these systems through the production of H(2)S. The physiological functions of H(2)S are mediated by different molecular targets, such as different ion channels and signaling proteins. Alternations of H(2)S metabolism lead to an array of pathological disturbances in the form of hypertension, atherosclerosis, heart failure, diabetes, cirrhosis, inflammation, sepsis, neurodegenerative disease, erectile dysfunction, and asthma, to name a few. Many new technologies have been developed to detect endogenous H(2)S production, and novel H(2)S-delivery compounds have been invented to aid therapeutic intervention of diseases related to abnormal H(2)S metabolism. While acknowledging the challenges ahead, research on H(2)S physiology and medicine is entering an exponential exploration era.