Heat shock prevents simulated ischemia-induced apoptosis in renal tubular cells via a PKC-dependent mechanism

Heat shock produces cellular tolerance to a variety of adverse conditions; however, the protective effect of heat shock on renal cell ischemic injury remains unclear. Protein kinase C (PKC) has been implicated in the signaling mechanisms of acute preconditioning, yet it remains unknown whether PKC mediates heat shock-induced delayed preconditioning in renal cells. To study this, renal tubular cells (LLC-PK1) were exposed to thermal stress (43°C) for 1 h and heat shock protein (HSP) 72 induction was confirmed by Western blot analysis. Cells were subjected to simulated ischemia 24 h after thermal stress, and the effect of heat shock (delayed preconditioning) on ischemia-induced apoptosis (terminal deoxynucleotidyl transferase dUTP nick-end labeling) and B cell lymphoma 2 (Bcl2) expression (Western) was determined. Subsequently, the effect of PKC inhibition on HSP72 induction and heat stress-induced ischemic tolerance was evaluated. Thermal stress induced HSP72 production, increased Bcl2 expression, and prevented simulated ischemia-induced renal tubular cell apoptosis. PKC inhibition abolished thermal induction of HSP72 and prevented heat stress-induced ischemic tolerance. These data demonstrate that thermal stress protects renal tubular cells from simulated ischemia-induced apoptosis through a PKC-dependent mechanism.

Download Full-text

T cells reactive to an inducible heat shock protein induce disease in toxin-induced interstitial nephritis.

Journal of Experimental Medicine ◽

10.1084/jem.180.6.2239 ◽

1994 ◽

Vol 180 (6) ◽

pp. 2239-2250 ◽

Cited By ~ 29

Author(s):

R A Weiss ◽

M P Madaio ◽

J E Tomaszewski ◽

C J Kelly

Keyword(s):

T Cells ◽

T Cell ◽

Heat Shock ◽

Mononuclear Cell ◽

Interstitial Nephritis ◽

Hsp70 Expression ◽

Tubular Cells ◽

Renal Tubular Cells ◽

Renal Tubular ◽

Mononuclear Cell Infiltrates

T cells reactive against immunodominant regions of inducible heat shock proteins (HSPs) have been identified in the chronic inflammatory lesions of several experimental autoimmune diseases. Since HSPs are known to be induced by a number of renal tubular epithelial cell toxins associated with chronic interstitial nephritis, we investigated the relevance of HSP expression and T cell reactivity to HSP70 in a model of progressive inflammatory interstitial nephritis. Chronic administration of cadmium chloride (CdCl2) to SJL/J mice induces HSP70 expression in renal tubular cells 4-5 wk before the development of interstitial mononuclear cell infiltrates. CdCl2 also induces HSP70 expression in cultured tubular epithelial cells from SJL/J mice. CD4+, TCR-alpha/beta+ T cell lines specific for an immunodominant HSP peptide are cytotoxic to heat stressed or CdCl2-treated renal tubular cells. Such HSP-reactive T cells mediate an inflammatory interstitial nephritis after adoptive transfer to CdCl2-treated mice at a time when immunoreactive HSP70 is detectable in the kidneys, but before the development of interstitial mononuclear cell infiltrates. T cells isolated from the nephritic kidneys of mice treated with CdCl2 for 13 wk are also cytotoxic to heat shocked or cadmium-treated tubular cells. These kidney-derived T cells additionally induced interstitial nephritis after passive transfer, indicating their pathogenic significance. Our studies strongly support a role for HSP-reactive T cells in CdCl2-induced interstitial nephritis and suggest that the induction of HSPs in the kidney by a multitude of "non-immune" events may initiate or facilitate inflammatory damage by HSP-reactive lymphocytes.

Download Full-text

Small Heat Shock Protein Beta-1 (HSPB1) Is Upregulated and Regulates Autophagy and Apoptosis of Renal Tubular Cells in Acute Kidney Injury

PLoS ONE ◽

10.1371/journal.pone.0126229 ◽

2015 ◽

Vol 10 (5) ◽

pp. e0126229 ◽

Cited By ~ 32

Author(s):

Tatsuki Matsumoto ◽

Madoka Urushido ◽

Haruna Ide ◽

Masayuki Ishihara ◽

Kazu Hamada-Ode ◽

...

Keyword(s):

Acute Kidney Injury ◽

Heat Shock ◽

Heat Shock Protein ◽

Kidney Injury ◽

Small Heat Shock Protein ◽

Tubular Cells ◽

Renal Tubular Cells ◽

Renal Tubular

Download Full-text

Naproxen-induced Ca2+ movement and death in MDCK canine renal tubular cells

Human & Experimental Toxicology ◽

10.1177/0960327115569810 ◽

2015 ◽

Vol 34 (11) ◽

pp. 1096-1105

Author(s):

H-H Cheng ◽

C-T Chou ◽

T-K Sun ◽

W-Z Liang ◽

J-S Cheng ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Annexin V ◽

Dependent Manner ◽

Acetoxymethyl Ester ◽

Concentration Dependent Manner ◽

Tubular Cells ◽

Renal Tubular Cells ◽

Renal Tubular ◽

Induced Apoptosis ◽

Darby Canine Kidney

Naproxen is an anti-inflammatory drug that affects cellular calcium ion (Ca2+) homeostasis and viability in different cells. This study explored the effect of naproxen on [Ca2+]i and viability in Madin-Darby canine kidney cells (MDCK) canine renal tubular cells. At concentrations between 50 μM and 300 μM, naproxen induced [Ca2+]i rises in a concentration-dependent manner. This Ca2+ signal was reduced partly when extracellular Ca2+ was removed. The Ca2+ signal was inhibited by a Ca2+ channel blocker nifedipine but not by store-operated Ca2+ channel inhibitors (econazole and SKF96365), a protein kinase C (PKC) activator phorbol 12-myristate 13-acetate, and a PKC inhibitor GF109203X. In Ca2+-free medium, pretreatment with 2,5-di-tert-butylhydroquinone or thapsigargin, an inhibitor of endoplasmic reticulum Ca2+ pumps, partly inhibited naproxen-induced Ca2+ signal. Inhibition of phospholipase C with U73122 did not alter naproxen-evoked [Ca2+]i rises. At concentrations between 15 μM and 30 μM, naproxen killed cells in a concentration-dependent manner, which was not reversed by prechelating cytosolic Ca2+ with the acetoxymethyl ester of 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid acetoxymethyl. Annexin V/propidium iodide staining data suggest that naproxen induced apoptosis. Together, in MDCK renal tubular cells, naproxen induced [Ca2+]i rises by inducing Ca2+ release from multiple stores that included the endoplasmic reticulum and Ca2+ entry via nifedipine-sensitive Ca2+ channels. Naproxen induced cell death that involved apoptosis.

Download Full-text