Klotho ameliorates chemically induced endoplasmic reticulum (ER) stress signaling

Srijita Banerjee, Yanhua Zhao, Partha Sarkar, Kevin P. Rosenblatt, Ronald Tilton, Sanjeev Choudhary

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background: Both endoplasmic reticulum (ER) stress, a fundamental cell response associated with stress-initiated unfolded protein response (UPR), and loss of Klotho, an anti-aging hormone linked to NF-κB-induced inflammation, occur in chronic metabolic diseases such as obesity and type 2 diabetes. We investigated if the loss of Klotho is causally linked to increased ER stress. Methods: We treated human renal epithelial HK-2, alveolar epithelial A549, HEK293, and SH-SH-SY5Y neuroblastoma cells with ER stress-inducing agents, thapsigargin and/or tunicamycin. Effects of overexpression or siRNA-mediated knockdown of Klotho on UPR signaling was investigated by immunoblotting and Real-time PCR. Results: Elevated Klotho levels in HK-2 cells decreased expression of ER stress markers phospho-IRE1, XBP-1s, BiP, CHOP, pJNK, and phospho-p38, all of which were elevated in response to tunicamycin and/or thapsigargin. Similar results were observed using A549 cells for XBP-1s, BiP, and CHOP in response to thapsigargin. Conversely, knockdown of Klotho in HEK 293 cells using siRNA caused further thapsigargin-induced increases in pIRE-1, XBP-1s, and BiP. Klotho overexpression in A549 cells blocked thapsigargin-induced caspase and PARP cleavage and improved cell viability. Conclusion: Our data indicate that Klotho has an important role in regulating ER stress and that loss of Klotho is causally linked to ER stress-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)659-672
Number of pages14
JournalCellular Physiology and Biochemistry
Volume31
Issue number4-5
DOIs
StatePublished - May 2013

Fingerprint

Endoplasmic Reticulum Stress
Thapsigargin
Unfolded Protein Response
Tunicamycin
Small Interfering RNA
HEK293 Cells
Metabolic Diseases
Caspases
Neuroblastoma
Immunoblotting
Type 2 Diabetes Mellitus
Real-Time Polymerase Chain Reaction
Cell Survival
Chronic Disease
Obesity
Hormones
Apoptosis
Inflammation
Kidney

Keywords

  • ER stress
  • Klotho
  • Thapsigargin
  • Tunicamycin
  • Unfolded protein response

ASJC Scopus subject areas

  • Physiology

Cite this

Klotho ameliorates chemically induced endoplasmic reticulum (ER) stress signaling. / Banerjee, Srijita; Zhao, Yanhua; Sarkar, Partha; Rosenblatt, Kevin P.; Tilton, Ronald; Choudhary, Sanjeev.

In: Cellular Physiology and Biochemistry, Vol. 31, No. 4-5, 05.2013, p. 659-672.

Research output: Contribution to journalArticle

Banerjee, Srijita ; Zhao, Yanhua ; Sarkar, Partha ; Rosenblatt, Kevin P. ; Tilton, Ronald ; Choudhary, Sanjeev. / Klotho ameliorates chemically induced endoplasmic reticulum (ER) stress signaling. In: Cellular Physiology and Biochemistry. 2013 ; Vol. 31, No. 4-5. pp. 659-672.
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