Choi, Young-Eun Kim, Mi-Soon Ha, Yuna Cho, Yoon Kim, Jang Kyun Rhee, Jae-Sung Ryu, Jae-Chun Kim, Youn-Jung 2024-01-19T11:03:14Z 2024-01-19T11:03:14Z 2022-04-07 2022-10 1738-642X https://pubs.kist.re.kr/handle/201004/114542 Background Nephrotoxicity is often referred to as a side effect of most drugs, but methods for effectively detecting nephrotoxicants still require development. Objective In this study, we identified the characteristic cellular responses and target genes affected by three nephrotoxic drugs (cisplatin, amphotericin B, and geneticin) using human oligonucleotide microarray and applied these genes to nephrotoxicity assessment in human kidney proximal tubular cells (HK-2). Results Through analysis of the gene expression profiles, it was identified 21 up- and 58 down-regulated genes changed by all three nephrotoxicants. Especially, the nephrotoxicants induced an increase in expression of a family of growth arrest and DNA-damage (GADD)-inducible genes (GADD34, GADD45A, GADD45G, and GADD153). In addition, these nephrotoxicants induced phosphorylation of p38 MAPK, which acts upstream of the GADD-related apoptosis pathway. The influence of other types of nephrotoxicants on expression of GADD family genes was also examined. Conclusion Our findings support that cisplatin, amphotericin B, and geneticin mediate induction of the GADD family of genes via the p38 MAPK pathway, resulting in the induction of apoptosis in HK-2 cells. We suggest that the apoptosis-related genes GADD45A and GADD153 may be reasonable candidate biomarkers for the screening of nephrotoxicity of drugs. English 대한독성 유전단백체 학회 Association of expression of GADD family genes and apoptosis in human kidney proximal tubular (HK-2) cells exposed to nephrotoxic drugs Article 10.1007/s13273-022-00231-3 1 Molecular & Cellular Toxicology, v.18, no.4, pp.569 - 580 Molecular & Cellular Toxicology 18 4 569 580 N scie scopus kci ART002878213 000772260100001 Biochemistry & Molecular Biology Toxicology Biochemistry & Molecular Biology Toxicology Article; Early Access ENDOPLASMIC-RETICULUM STRESS IN-VIVO ACTIVATION BIOMARKERS CARBOPLATIN OCHRATOXIN RADIATION TOXICITY PROTEINS SURVIVAL Nephrotoxicity Cisplatin Amphotericin B Geneticin Apoptosis GADD family genes