PMID- 35406792
OWN - NLM
STAT- MEDLINE
DCOM- 20221213
LR  - 20221213
IS  - 2073-4409 (Electronic)
IS  - 2073-4409 (Linking)
VI  - 11
IP  - 7
DP  - 2022 Apr 5
TI  - D-Cysteine Activates Chaperone-Mediated Autophagy in Cerebellar Purkinje Cells 
      via the Generation of Hydrogen Sulfide and Nrf2 Activation.
LID - 10.3390/cells11071230 [doi]
LID - 1230
AB  - Chaperone-mediated autophagy (CMA) is a pathway in the autophagy-lysosome protein 
      degradation system. CMA impairment has been implicated to play a role in 
      spinocerebellar ataxia (SCA) pathogenesis. D-cysteine is metabolized by D-amino 
      acid oxidase (DAO), leading to hydrogen sulfide generation in the cerebellum. 
      Although D-cysteine alleviates the disease phenotypes in SCA-model mice, it 
      remains unknown how hydrogen sulfide derived from D-cysteine exerts this effect. 
      In the present study, we investigated the effects of D-cysteine and hydrogen 
      sulfide on CMA activity using a CMA activity marker that we have established. 
      D-cysteine activated CMA in Purkinje cells (PCs) of primary cerebellar cultures 
      where DAO was expressed, while it failed to activate CMA in DAO-deficient AD293 
      cells. In contrast, Na(2)S, a hydrogen sulfide donor, activated CMA in both PCs 
      and AD293 cells. Nuclear factor erythroid 2-related factor 2 (Nrf2) is known to 
      be activated by hydrogen sulfide and regulate CMA activity. An Nrf2 inhibitor, 
      ML385, prevented CMA activation triggered by D-cysteine and Na(2)S. Additionally, 
      long-term treatment with D-cysteine increased the amounts of Nrf2 and LAMP2A, a 
      CMA-related protein, in the mouse cerebellum. These findings suggest that 
      hydrogen sulfide derived from D-cysteine enhances CMA activity via Nrf2 
      activation.
FAU - Ueda, Erika
AU  - Ueda E
AD  - Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical 
      Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
FAU - Ohta, Tomoko
AU  - Ohta T
AD  - Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical 
      Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
FAU - Konno, Ayumu
AU  - Konno A
AUID- ORCID: 0000-0001-9382-396X
AD  - Department of Neurophysiology & Neural Repair, Graduate School of Medicine, Gunma 
      University, Maebashi 371-8511, Japan.
FAU - Hirai, Hirokazu
AU  - Hirai H
AUID- ORCID: 0000-0002-0721-4293
AD  - Department of Neurophysiology & Neural Repair, Graduate School of Medicine, Gunma 
      University, Maebashi 371-8511, Japan.
FAU - Kurauchi, Yuki
AU  - Kurauchi Y
AD  - Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical 
      Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
FAU - Katsuki, Hiroshi
AU  - Katsuki H
AUID- ORCID: 0000-0001-7595-3154
AD  - Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical 
      Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
FAU - Seki, Takahiro
AU  - Seki T
AUID- ORCID: 0000-0002-9894-4768
AD  - Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical 
      Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220405
PL  - Switzerland
TA  - Cells
JT  - Cells
JID - 101600052
RN  - K848JZ4886 (Cysteine)
RN  - YY9FVM7NSN (Hydrogen Sulfide)
RN  - 0 (NF-E2-Related Factor 2)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Chaperone-Mediated Autophagy
MH  - Cysteine/metabolism/pharmacology
MH  - *Hydrogen Sulfide/metabolism/pharmacology
MH  - NF-E2-Related Factor 2/metabolism
MH  - Purkinje Cells
PMC - PMC8997644
OTO - NOTNLM
OT  - Nrf2
OT  - aromatic-turmerone
OT  - dopaminergic neurons
OT  - microglia
COIS- The authors declare no conflict of interest.
EDAT- 2022/04/13 06:00
MHDA- 2022/04/14 06:00
PMCR- 2022/04/05
CRDT- 2022/04/12 01:05
PHST- 2022/03/04 00:00 [received]
PHST- 2022/04/04 00:00 [revised]
PHST- 2022/04/04 00:00 [accepted]
PHST- 2022/04/12 01:05 [entrez]
PHST- 2022/04/13 06:00 [pubmed]
PHST- 2022/04/14 06:00 [medline]
PHST- 2022/04/05 00:00 [pmc-release]
AID - cells11071230 [pii]
AID - cells-11-01230 [pii]
AID - 10.3390/cells11071230 [doi]
PST - epublish
SO  - Cells. 2022 Apr 5;11(7):1230. doi: 10.3390/cells11071230.