Hydrogen sulfide is an endogenous gasotransmitter and its mechanism of action involves activation of ATP-sensitive K+ channels and phosphodiesterase inhibition. As both mechanisms are potentially involved in malignant hyperthermia (MH), in the present study we addressed the involvement of the L-cysteine/hydrogen sulfide pathway in MH. Skeletal muscle biopsies obtained from 25 MH-susceptible (MHS) and 56 MH-negative (MHN) individuals have been used to perform the in vitro contracture test (IVCT). Quantitative real-time PCR (qPCR) and Western blotting studies have also been performed. Hydrogen sulfide levels are measured in both tissue samples and plasma. In MHS biopsies an increase in cystathionine β-synthase (CBS) occurs, as both mRNA and protein expression compared with MHN biopsies. Hydrogen sulfide biosynthesis is increased in MHS biopsies (0.128±0.12 compared with 0.943±0.13 nmol/mg of protein per min for MHN and MHS biopsies, respectively; P<0.01). Addition of sodium hydrosulfide (NaHS) to MHS samples evokes a response similar, in the IVCT, to that elicited by either caffeine or halothane. Incubation of MHN biopsies with NaHS, before caffeine or halothane challenge, switches an MHN to an MHS response. In conclusion we demonstrate the involvement of the L-cysteine/hydrogen sulfide pathway in MH, giving new insight into MH molecular mechanisms. This finding has potential implications for clinical care and could help to define less invasive diagnostic procedures.
Skip Nav Destination
Article navigation
January 2016
-
Cover Image
Cover Image
Representative photograph of Massons's trichrome-stained section of an epidermal wound in a mouse with streptozotocin-induced diabetes treated with a kinin B2 receptor antagonist. For further information please see pp. 45-56. Original image courtesy of D. Desposito, C. Chollet, C. Taveau, V. Descamps, F. Alhenc-Gelas, R. Roussel, N. Bouby and L. Waeckel.
Research Article|
November 30 2015
Cystathionine β-synthase-derived hydrogen sulfide is involved in human malignant hyperthermia
Valentina Vellecco;
Valentina Vellecco
1
*Department of Pharmacy, University of Naples ‘Federico II’, Naples, Italy
Search for other works by this author on:
Antonio Mancini;
Antonio Mancini
1
†Centre of Biotechnology, Cardarelli Hospital, Naples, Italy
Search for other works by this author on:
Angela Ianaro;
Angela Ianaro
*Department of Pharmacy, University of Naples ‘Federico II’, Naples, Italy
Search for other works by this author on:
Vincenzo Calderone;
Vincenzo Calderone
‡Department of Pharmacy, University of Pisa, Pisa, Italy
Search for other works by this author on:
Chiara Attanasio;
Chiara Attanasio
§Centre for Advanced Biomaterials for Health Care (CRIB), Italian Institute of Technology, Naples, Italy
Search for other works by this author on:
Anna Cantalupo;
Anna Cantalupo
*Department of Pharmacy, University of Naples ‘Federico II’, Naples, Italy
¶Weill Cornell University Medical College, New York City, NY 10065, U.S.A.
Search for other works by this author on:
Barbara Andria;
Barbara Andria
†Centre of Biotechnology, Cardarelli Hospital, Naples, Italy
Search for other works by this author on:
Gennaro Savoia;
Gennaro Savoia
║Unit of Anaesthesiology and Resuscitation IV, Cardarelli Hospital, Naples, Italy
Search for other works by this author on:
Elisabetta Panza;
Elisabetta Panza
*Department of Pharmacy, University of Naples ‘Federico II’, Naples, Italy
Search for other works by this author on:
Antonietta Di Martino;
Antonietta Di Martino
†Centre of Biotechnology, Cardarelli Hospital, Naples, Italy
Search for other works by this author on:
Giuseppe Cirino;
*Department of Pharmacy, University of Naples ‘Federico II’, Naples, Italy
Correspondence: Professor Giuseppe Cirino (email cirino@unina.it).
Search for other works by this author on:
Mariarosaria Bucci
Mariarosaria Bucci
*Department of Pharmacy, University of Naples ‘Federico II’, Naples, Italy
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
July 24 2015
Revision Received:
October 02 2015
Accepted:
October 12 2015
Accepted Manuscript online:
October 12 2015
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 Authors; published by Portland Press Limited
2016
Clin Sci (Lond) (2016) 130 (1): 35–44.
Article history
Received:
July 24 2015
Revision Received:
October 02 2015
Accepted:
October 12 2015
Accepted Manuscript online:
October 12 2015
Citation
Valentina Vellecco, Antonio Mancini, Angela Ianaro, Vincenzo Calderone, Chiara Attanasio, Anna Cantalupo, Barbara Andria, Gennaro Savoia, Elisabetta Panza, Antonietta Di Martino, Giuseppe Cirino, Mariarosaria Bucci; Cystathionine β-synthase-derived hydrogen sulfide is involved in human malignant hyperthermia. Clin Sci (Lond) 1 January 2016; 130 (1): 35–44. doi: https://doi.org/10.1042/CS20150521
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.