PMID- 34174560
OWN - NLM
STAT- MEDLINE
DCOM- 20210727
LR  - 20231107
IS  - 2213-2317 (Electronic)
IS  - 2213-2317 (Linking)
VI  - 45
DP  - 2021 Sep
TI  - Duchenne's muscular dystrophy involves a defective transsulfuration pathway 
      activity.
PG  - 102040
LID - S2213-2317(21)00199-3 [pii]
LID - 10.1016/j.redox.2021.102040 [doi]
LID - 102040
AB  - Duchenne muscular dystrophy (DMD) is the most frequent X chromosome-linked 
      disease caused by mutations in the gene encoding for dystrophin, leading to 
      progressive and unstoppable degeneration of skeletal muscle tissues. Despite 
      recent advances in the understanding of the molecular processes involved in the 
      pathogenesis of DMD, there is still no cure. In this study, we aim at 
      investigating the potential involvement of the transsulfuration pathway (TSP), 
      and its by-end product namely hydrogen sulfide (H(2)S), in primary human 
      myoblasts isolated from DMD donors and skeletal muscles of dystrophic (mdx) mice. 
      In myoblasts of DMD donors, we demonstrate that the expression of key genes 
      regulating the H(2)S production and TSP activity, including cystathionine gamma lyase 
      (CSE), cystathionine beta-synthase (CBS), 3 mercaptopyruvate sulfurtransferase 
      (3-MST), cysteine dioxygenase (CDO), cysteine sulfonic acid decarboxylase (CSAD), 
      glutathione synthase (GS) and gamma -glutamylcysteine synthetase (gamma-GCS) is reduced. 
      Starting from these findings, using Nuclear Magnetic Resonance (NMR) and 
      quantitative Polymerase Chain Reaction (qPCR) we show that the levels of 
      TSP-related metabolites such as methionine, glycine, glutathione, glutamate and 
      taurine, as well as the expression levels of the aforementioned TSP related 
      genes, are significantly reduced in skeletal muscles of mdx mice compared to 
      healthy controls, at both an early (7 weeks) and overt (17 weeks) stage of the 
      disease. Importantly, the treatment with sodium hydrosulfide (NaHS), a commonly 
      used H(2)S donor, fully recovers the impaired locomotor activity in both 7 and 17 
      old mdx mice. This is an effect attributable to the reduced expression of 
      pro-inflammatory markers and restoration of autophagy in skeletal muscle tissues. 
      In conclusion, our study uncovers a defective TSP pathway activity in DMD and 
      highlights the role of H(2)S-donors for novel and safe adjuvant therapy to treat 
      symptoms of DMD.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Panza, E
AU  - Panza E
AD  - Department of Pharmacy, School of Medicine and Surgery, University of Naples 
      Federico II, Naples, Italy.
FAU - Vellecco, V
AU  - Vellecco V
AD  - Department of Pharmacy, School of Medicine and Surgery, University of Naples 
      Federico II, Naples, Italy.
FAU - Iannotti, F A
AU  - Iannotti FA
AD  - Institute of Biomolecular Chemistry (ICB), National Research Council (CNR), 
      Pozzuoli (NA), Italy.
FAU - Paris, D
AU  - Paris D
AD  - Institute of Biomolecular Chemistry (ICB), National Research Council (CNR), 
      Pozzuoli (NA), Italy.
FAU - Manzo, O L
AU  - Manzo OL
AD  - Department of Pharmacy, School of Medicine and Surgery, University of Naples 
      Federico II, Naples, Italy; Center for Vascular Biology, Department of Pathology 
      and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New 
      York, NY, USA.
FAU - Smimmo, M
AU  - Smimmo M
AD  - Department of Pharmacy, School of Medicine and Surgery, University of Naples 
      Federico II, Naples, Italy.
FAU - Mitilini, N
AU  - Mitilini N
AD  - UOSC, Pathological Anatomy, A. Cardarelli Hospital, Naples, Italy.
FAU - Boscaino, A
AU  - Boscaino A
AD  - UOSC, Pathological Anatomy, A. Cardarelli Hospital, Naples, Italy.
FAU - de Dominicis, G
AU  - de Dominicis G
AD  - UOSC, Pathological Anatomy, A. Cardarelli Hospital, Naples, Italy.
FAU - Bucci, M
AU  - Bucci M
AD  - Department of Pharmacy, School of Medicine and Surgery, University of Naples 
      Federico II, Naples, Italy. Electronic address: mrbucci@unina.it.
FAU - Di Lorenzo, A
AU  - Di Lorenzo A
AD  - Center for Vascular Biology, Department of Pathology and Laboratory Medicine, 
      Weill Cornell Medical College, Cornell University, New York, NY, USA.
FAU - Cirino, G
AU  - Cirino G
AD  - Department of Pharmacy, School of Medicine and Surgery, University of Naples 
      Federico II, Naples, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210619
PL  - Netherlands
TA  - Redox Biol
JT  - Redox biology
JID - 101605639
RN  - EC 4.4.1.1 (Cystathionine gamma-Lyase)
SB  - IM
MH  - Animals
MH  - Cystathionine gamma-Lyase/genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred mdx
MH  - Muscle, Skeletal
MH  - *Muscular Dystrophy, Duchenne/genetics
PMC - PMC8246642
OTO - NOTNLM
OT  - Autophagy
OT  - Duchenne muscular dystrophy
OT  - H(2)S donors
OT  - Inflammation
OT  - Sodium hydrosulfide (NaHS)
COIS- The authors declare no conflict of interest.
EDAT- 2021/06/27 06:00
MHDA- 2021/07/28 06:00
PMCR- 2021/06/19
CRDT- 2021/06/26 20:18
PHST- 2021/02/12 00:00 [received]
PHST- 2021/05/20 00:00 [revised]
PHST- 2021/06/07 00:00 [accepted]
PHST- 2021/06/27 06:00 [pubmed]
PHST- 2021/07/28 06:00 [medline]
PHST- 2021/06/26 20:18 [entrez]
PHST- 2021/06/19 00:00 [pmc-release]
AID - S2213-2317(21)00199-3 [pii]
AID - 102040 [pii]
AID - 10.1016/j.redox.2021.102040 [doi]
PST - ppublish
SO  - Redox Biol. 2021 Sep;45:102040. doi: 10.1016/j.redox.2021.102040. Epub 2021 Jun 
      19.