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ZAC1 is up‐regulated by hypertonicity and decreases sorbitol dehydrogenase expression allowing accumulation of sorbitol in kidney cells
Author(s) -
Lanaspa Miguel Angel,
AndresHernando Ana,
Dai Yue,
Li Nanxing,
Berl Tomas,
Rivard Christopher John
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.1001.8
Subject(s) - sorbitol dehydrogenase , sorbitol , downregulation and upregulation , biology , western blot , gene knockdown , endocrinology , medicine , microbiology and biotechnology , chemistry , apoptosis , biochemistry , gene
The zinc‐finger protein ZAC1 was determined to be markedly upregulated under hypertonic stress in inner medullary collecting duct (IMCD3) cells by Affymetrix genechip analysis (219‐fold, p<0.001). This change in message was verified by Quantitative PCR and by Western blot for protein. In mouse and human kidney tissues, ZAC1 expression was substantial in the papilla and absent in the cortex. ZAC1 protein expression was localized to the nucleus in cells under hypertonic stress by immunocytochemical analysis. Since a previous study in the hippocampal cell line HW3‐5 reported an inverse correlation between the expression of ZAC1 and sorbitol dehydrogenase (SDH), ‐a key enzyme involved in sorbitol degradation that is down regulated with hypertonicity. We examined if the decrease in SDH expression under hypertonic stress is mediated by the up‐regulation of ZAC1. Stable IMCD3 clones silenced for ZAC1 to varying levels demonstrated a direct effect on SDH expression. Silencing ZAC1 expression under hypertonic conditions caused maintenance of high SDH protein expression which prevented sorbitol accumulation in IMCD3 cells. Taken together, these data indicates that ZAC1 is up‐regulated under hypertonic stress and negatively regulates expression of SDH allowing for accumulation of sorbitol as a compatible organic osmolyte.