PMID- 21793897
OWN - NLM
STAT- MEDLINE
DCOM- 20120618
LR  - 20211203
IS  - 1600-079X (Electronic)
IS  - 0742-3098 (Linking)
VI  - 52
IP  - 1
DP  - 2012 Jan
TI  - Melatonin alleviates cadmium-induced cellular stress and germ cell apoptosis in 
      testes.
PG  - 71-9
LID - 10.1111/j.1600-079X.2011.00921.x [doi]
AB  - Increasing evidence demonstrates that melatonin has an anti-apoptotic effect in 
      somatic cells. However, whether melatonin can protect against germ cell apoptosis 
      remains obscure. Cadmium (Cd) is a testicular toxicant and induces germ cell 
      apoptosis. In this study, we investigated the effects of melatonin on Cd-evoked 
      germ cell apoptosis in testes. Male ICR mice were intraperitoneally (i.p.) 
      injected with melatonin (5 mg/kg) every 8 hr, beginning at 8 hr before CdCl(2) 
      (2.0 mg/kg, i.p.). As expected, acute Cd exposure resulted in germ cell apoptosis 
      in testes, as determined by terminal dUTP nick-end labeling (TUNEL) staining. 
      Melatonin significantly alleviated Cd-induced testicular germ cell apoptosis. An 
      additional experiment showed that spliced form of XBP-1, the target of the IRE-1 
      pathway, was significantly increased in testes of mice injected with CdCl(2). 
      GRP78, an endoplasmic reticulum (ER) chaperone, and CHOP, a downstream target of 
      the PERK pathway, were upregulated in testes of Cd-treated mice. In addition, 
      acute Cd exposure significantly increased testicular eIF2alpha and JNK 
      phosphorylation, indicating that the unfolded protein response (UPR) pathway was 
      activated by CdCl(2). Interestingly, melatonin almost completely inhibited 
      Cd-induced ER stress and the UPR in testes. In addition, melatonin obviously 
      attenuated Cd-induced heme oxygenase (HO)-1 expression and protein nitration in 
      testes. Taken together, these results suggest that melatonin alleviates 
      Cd-induced cellular stress and germ cell apoptosis in testes. Melatonin may be 
      useful as pharmacological agents to protect against Cd-induced testicular 
      toxicity.
CI  - (c) 2011 John Wiley & Sons A/S.
FAU - Ji, Yan-Li
AU  - Ji YL
AD  - Department of Toxicology, Anhui Medical University, Hefei, China.
FAU - Wang, Hua
AU  - Wang H
FAU - Meng, Can
AU  - Meng C
FAU - Zhao, Xian-Feng
AU  - Zhao XF
FAU - Zhang, Cheng
AU  - Zhang C
FAU - Zhang, Ying
AU  - Zhang Y
FAU - Zhao, Mei
AU  - Zhao M
FAU - Chen, Yuan-Hua
AU  - Chen YH
FAU - Meng, Xiu-Hong
AU  - Meng XH
FAU - Xu, De-Xiang
AU  - Xu DX
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110728
PL  - England
TA  - J Pineal Res
JT  - Journal of pineal research
JID - 8504412
RN  - 0 (Antioxidants)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (Hspa5 protein, mouse)
RN  - 0 (Regulatory Factor X Transcription Factors)
RN  - 0 (Transcription Factors)
RN  - 0 (X-Box Binding Protein 1)
RN  - 0 (Xbp1 protein, mouse)
RN  - 00BH33GNGH (Cadmium)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - JL5DK93RCL (Melatonin)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Antioxidants/pharmacology
MH  - Apoptosis/*drug effects
MH  - Cadmium/*toxicity
MH  - DNA-Binding Proteins/metabolism
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - Endoplasmic Reticulum Stress/*drug effects
MH  - Germ Cells/chemistry/cytology/metabolism
MH  - Heme Oxygenase-1/metabolism
MH  - Histocytochemistry
MH  - In Situ Nick-End Labeling
MH  - Male
MH  - Melatonin/*pharmacology
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Regulatory Factor X Transcription Factors
MH  - Testis/chemistry/cytology/*drug effects/metabolism
MH  - Transcription Factors/metabolism
MH  - X-Box Binding Protein 1
EDAT- 2011/07/29 06:00
MHDA- 2012/06/19 06:00
CRDT- 2011/07/29 06:00
PHST- 2011/07/29 06:00 [entrez]
PHST- 2011/07/29 06:00 [pubmed]
PHST- 2012/06/19 06:00 [medline]
AID - 10.1111/j.1600-079X.2011.00921.x [doi]
PST - ppublish
SO  - J Pineal Res. 2012 Jan;52(1):71-9. doi: 10.1111/j.1600-079X.2011.00921.x. Epub 
      2011 Jul 28.