Endothelin receptor-specific control of endoplasmic reticulum stress and apoptosis in the kidney

Carmen De Miguel, William C. Hamrick, Janet L. Hobbs, David M. Pollock, Pamela K Carmines, Jennifer S. Pollock

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Endothelin-1 (ET-1) promotes renal damage during cardiovascular disease; yet, the molecular mechanisms involved remain unknown. Endoplasmic reticulum (ER) stress, triggered by unfolded protein accumulation in the ER, contributes to apoptosis and organ injury. These studies aimed to determine whether the ET-1 system promotes renal ER stress development in response to tunicamycin. ET B deficient (ET B def) or transgenic control (TG-con) rats were used in the presence or absence of ET A receptor antagonism. Tunicamycin treatment similarly increased cortical ER stress markers in both rat genotypes; however, only ET B def rats showed a 14-24 fold increase from baseline for medullary GRP78, sXBP-1, and CHOP. Pre-treatment of TG-con rats with the ET A blocker ABT-627 for 1 week prior to tunicamycin injection significantly reduced the ER stress response in cortex and medulla, and also inhibited renal apoptosis. Pre-treatment with ABT-627 failed to decrease renal ER stress and apoptosis in ET B def rats. In conclusion, the ET-1 system is important for the development of tunicamycin-induced renal ER stress and apoptosis. ET A receptor activation induces renal ER stress genes and apoptosis, while functional activation of the ET B receptor has protective effects. These results highlight targeting the ET A receptor as a therapeutic approach against ER stress-induced kidney injury.

Original languageEnglish (US)
Article number43152
JournalScientific reports
Volume7
DOIs
StatePublished - Feb 23 2017

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Endothelin Receptors
Endoplasmic Reticulum Stress
Apoptosis
Kidney
Tunicamycin
Endothelin-1
Transgenic Rats
Protein Unfolding
Wounds and Injuries
Therapeutics
Endoplasmic Reticulum
Cardiovascular Diseases
Genotype
Injections

ASJC Scopus subject areas

  • General

Cite this

Endothelin receptor-specific control of endoplasmic reticulum stress and apoptosis in the kidney. / De Miguel, Carmen; Hamrick, William C.; Hobbs, Janet L.; Pollock, David M.; Carmines, Pamela K; Pollock, Jennifer S.

In: Scientific reports, Vol. 7, 43152, 23.02.2017.

Research output: Contribution to journalArticle

De Miguel, Carmen ; Hamrick, William C. ; Hobbs, Janet L. ; Pollock, David M. ; Carmines, Pamela K ; Pollock, Jennifer S. / Endothelin receptor-specific control of endoplasmic reticulum stress and apoptosis in the kidney. In: Scientific reports. 2017 ; Vol. 7.
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