Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26404762
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 276.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 276.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 276.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 276.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 276.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 276.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 276.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Deprecated: Implicit conversion from float 276.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534
Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\26404762
.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Arch+Toxicol
2016 ; 90
(9
): 2187-2200
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
2,3,5,6-Tetramethylpyrazine (TMP) down-regulated arsenic-induced heme oxygenase-1
and ARS2 expression by inhibiting Nrf2, NF-?B, AP-1 and MAPK pathways in human
proximal tubular cells
#MMPMID26404762
Gong X
; Ivanov VN
; Hei TK
Arch Toxicol
2016[Sep]; 90
(9
): 2187-2200
PMID26404762
show ga
Our recent study demonstrated that sodium arsenite at a clinically relevant dose
induced nephrotoxicity in human renal proximal tubular epithelial cell line HK-2,
which could be inhibited by natural product 2,3,5,6-tetramethylpyrazine (TMP)
with antioxidant activity. The present study demonstrated that arsenic exposure
resulted in protein and enzymatic induction of heme oxygenase-1 (HO-1) in dose-
and time-dependent manners in HK-2 cells. Blocking HO-1 enzymatic activity by
zinc protoporphyrin (ZnPP) augmented arsenic-induced apoptosis, ROS production
and mitochondrial dysfunction, suggesting a critical role for HO-1 as a renal
protectant in this procession. On the other hand, TMP, upstream of HO-1,
inhibited arsenic-induced ROS production and ROS-dependent HO-1 expression. TMP
also prevented mitochondria dysfunction and suppressed activation of the
intrinsic apoptotic pathway in HK-2 cells. Our results revealed that the
regulation of arsenic-induced HO-1 expression was performed through multiple
ROS-dependent signal pathways and the corresponding transcription factors,
including p38 MAPK and JNK (but not ERK), AP-1, Nrf2 and NF-?B. TMP inhibited
arsenic-induced activations of JNK, p38 MAPK, ERK, AP-1 and Nrf2 and block HO-1
protein expression. The present study, furthermore, demonstrated arsenic-induced
expression of arsenic response protein 2 (ARS2) that was regulated by p38 MAPK,
ERK and NF-?B. To our knowledge, this is the first report showing that ARS2
involved in arsenic-induced nephrotoxicity, while TMP pretreatment prevented such
an up-regulation of ARS2 in HK-2 cells. Given ARS2 and HO-1 sharing the similar
regulation mechanism, we speculated that ARS2 might also mediate cell survival in
this procession. In summary, our study highlighted a role of HO-1 in the
protection against arsenic-induced cytotoxicity downstream from the primary
targets of TMP and further indicated that TMP may be used as a potential
therapeutic agent in the treatment of arsenic-induced nephrotoxicity.