Journal
MOLECULAR MEDICINE REPORTS
Volume 13, Issue 5, Pages 4443-4450Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2016.5067
Keywords
CoCl2 treatment; Na+/H+ exchanger activity; intracellular pH; time-dependent manner
Categories
Funding
- Foundation from China Scholarship Council [201207045015]
- '5451' project of Henan Health Department [201201065]
- Foundation of Henan Educational Committee [12A310010, 16A310003]
- Foundation for University Key Teacher of Henan Educational Committee [2011GGJS-013]
- Science and Technology Planning Project of Henan [122300410338, 122300410082, 132300410029, 132102310138, 142102310140]
- Science and Technology Planning Project of Zhengzhou [10PTGS484-7, 121PPTGG507-22, 2PPTSF302, N201250105]
- National Natural Science Foundation of China [81500433]
Ask authors/readers for more resources
Hypoxia causes injury to the central nervous system during stroke and has significant effects on pH homeostasis. Na+/H+ exchanger isoform 1 (NHE1) is important in the mechanisms of hypoxia and intracellular pH (pHi) homeostasis. As a well-established hypoxia-mimetic agent, CoCl2 stabilizes and increases the expression of hypoxia inducible factor-1 alpha (HIF-1 alpha), which regulates several genes involved in pH balance, including NHE1. However, it is not fully understood whether NHE1 is activated in astrocytes under CoC(l)2 treatment. In the current study, pHi and NHE activity were analyzed using the pHi-sensitive dye BCECF-AM. Using cariporide (an NHE1-specific inhibitor) and EIPA (an NHE nonspecific inhibitor), the current study demonstrated that it was NHE1, not the other NHE isoforms, that was important in regulating pHi homeostasis in astrocytes during CoCl2 treatment. Additionally, the present study observed that, during the early period of CoCl2 treatment (the first 2 h), NHE1 activity and pHi dropped immediately, and NHE1 mRNA expression was reduced compared with control levels, whereas expression levels of the NHE1 protein had not yet changed. In the later period of CoCl2 treatment, NHE1 activity and pHi significantly increased compared with the control levels, as did the mRNA and protein expression levels of NHE1. Furthermore, the cell viability and injury of astrocytes was not changed during the initial 8 h of CoCl2 treatment; their deterioration was associated with the higher levels of pHi and NHE1 activity. The current study concluded that NHE1 activity and pHi homeostasis are regulated by CoCl2 treatment in a time-dependent manner in astrocytes, and may be responsible for the changes in cell viability and injury observed under hypoxia-mimetic conditions induced by CoCl2 treatment.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available