PMID- 31269461
OWN - NLM
STAT- MEDLINE
DCOM- 20200225
LR  - 20200225
IS  - 1638-6183 (Electronic)
IS  - 0300-9084 (Linking)
VI  - 165
DP  - 2019 Oct
TI  - Implication of homocysteine in protein quality control processes.
PG  - 19-31
LID - S0300-9084(19)30190-7 [pii]
LID - 10.1016/j.biochi.2019.06.017 [doi]
AB  - Homocysteine (Hcy) is a key metabolite generated during methionine metabolism. 
      The elevated levels of Hcy in the blood are reffered to as hyperhomocystenimeia 
      (HHcy). The HHcy is caused by impaired metabolism/deficiency of either folate or 
      B12 or defects in Hcy metabolism. Accumulating evidence suggests that HHcy is 
      associated with cardiovascular and brain diseases including atherosclerosis, 
      endothelial injury, and stroke etc. Vitamin B12 (cobalamin; B12) is a 
      water-soluble vitamin essential for two metabolic reactions. It acts as a 
      co-factor for methionine synthase and L-methylmalonyl-CoA mutase. Besides, it is 
      also vital for DNA synthesis and maturation of RBC. Deficiency of B12 is 
      associated with haematological and neurological disorders. Hyperhomocysteinemia 
      (HHcy)-induced toxicity is thought to be mediated by the accumulation of Hcy and 
      its metabolites, homocysteinylated proteins. Cellular protein quality control 
      (PQC) is essential for the maintenance of proteome integrity, and cell viability 
      and its failure contributes to the development of multiple diseases. Chaperones, 
      unfolded protein response (UPR), ubiquitin-proteasome system (UPS), and autophagy 
      are analogous strategies of PQC that maintain cellular proteome integrity. 
      Recently, multiple studies reported that HHcy responsible for perturbation of PQC 
      by reducing chaperone levels, activating UPR, and impairing autophagy. Besides, 
      HHcy also induce cytotoxicity, inflammation, protein aggregation and apoptosis. 
      It has been shown that some of the factors including altered SIRT1-HSF1 axis and 
      irreversible homocysteinylation of proteins are responsible for folate and/or B12 
      deficiency or HHcy-induced impairment of PQC. Therefore, this review highlights 
      the current understanding of HHcy in the context of cellular PQC and their 
      pathophysiological and clinical consequences, epigenomic changes, therapeutic 
      implications of B12, and chemical chaperones based on cell culture and 
      experimental animal models.
CI  - Copyright (c) 2019 Elsevier B.V. and Societe Francaise de Biochimie et Biologie 
      Moleculaire (SFBBM). All rights reserved.
FAU - Reddy, V Sudhakar
AU  - Reddy VS
AD  - Biochemistry Division, National Institute of Nutrition, Hyderabad, India. 
      Electronic address: sudhakarnin@gmail.com.
FAU - Trinath, Jamma
AU  - Trinath J
AD  - Department of Biological Sciences, BITS-Pilani, 500078, Hyderabad Campus, 
      Hyderabad, Telangana, India.
FAU - Reddy, G Bhanuprakash
AU  - Reddy GB
AD  - Biochemistry Division, National Institute of Nutrition, Hyderabad, India. 
      Electronic address: bhanu@ninindia.org.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20190630
PL  - France
TA  - Biochimie
JT  - Biochimie
JID - 1264604
RN  - 0 (Molecular Chaperones)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - P6YC3EG204 (Vitamin B 12)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Autophagy
MH  - Cell Line
MH  - Homocysteine/*metabolism
MH  - Humans
MH  - Hyperhomocysteinemia/*blood
MH  - Mice
MH  - Molecular Chaperones/metabolism
MH  - Protein Aggregation, Pathological
MH  - Protein Processing, Post-Translational
MH  - Rats
MH  - Ubiquitination
MH  - Unfolded Protein Response
MH  - Vitamin B 12/*metabolism
OTO - NOTNLM
OT  - Autophagy
OT  - Chaperones
OT  - Hyperhomocysteinemia
OT  - Unfolded protein response
OT  - Vitamin B12
EDAT- 2019/07/04 06:00
MHDA- 2020/02/26 06:00
CRDT- 2019/07/04 06:00
PHST- 2019/03/15 00:00 [received]
PHST- 2019/06/26 00:00 [accepted]
PHST- 2019/07/04 06:00 [pubmed]
PHST- 2020/02/26 06:00 [medline]
PHST- 2019/07/04 06:00 [entrez]
AID - S0300-9084(19)30190-7 [pii]
AID - 10.1016/j.biochi.2019.06.017 [doi]
PST - ppublish
SO  - Biochimie. 2019 Oct;165:19-31. doi: 10.1016/j.biochi.2019.06.017. Epub 2019 Jun 
      30.