Human liver-type fatty acid–binding protein protects against tubulointerstitial injury in aldosterone-induced renal injury

To demonstrate the renoprotective function of human liver-type fatty acid–binding protein (hL-FABP) expressed in proximal tubules in aldosterone (Aldo)-induced renal injury, hL-FABP chromosomal transgenic (Tg) and wild-type (WT) mice received systemic Aldo infusions (Tg-Aldo and WT-Aldo, respectively) were given 1% NaCl water for 28 days. In this model, elevation of systolic blood pressure, monocyte chemoattractant protein-1 expression, macrophage infiltration in the interstitium, tubulointerstitial damage, and depositions of type I and III collagens were observed. Elevation of systolic blood pressure did not differ in WT-Aldo vs. Tg-Aldo animals, however, renal injury was suppressed in Tg-Aldo compared with WT-Aldo mice. Dihydroethidium fluorescence was used to evaluate reactive oxidative stress, which was suppressed in Tg-Aldo compared with WT-Aldo mice. Gene expression of angiotensinogen in the kidney was upregulated, and excretion of urinary angiotensinogen was increased in WT-Aldo mice. This exacerbation was suppressed in Tg-Aldo mice. Expression of hL-FABP was upregulated in proximal tubules of Tg-Aldo mice. Urinary excretion of hL-FABP was significantly greater in Tg-Aldo than in Tg-control mice. In conclusion, hL-FABP ameliorated the tubulointerstitial damage in Aldo-induced renal injury via reducing oxidative stress and suppressing activation of the intrarenal renin-angiotensin system.

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Renoprotective effect of renal liver-type fatty acid binding protein and angiotensin II type 1a receptor loss in renal injury caused by RAS activation

AJP Renal Physiology ◽

10.1152/ajprenal.00460.2013 ◽

2014 ◽

Vol 306 (6) ◽

pp. F655-F663 ◽

Cited By ~ 9

Author(s):

Daisuke Ichikawa ◽

Atsuko Kamijo-Ikemori ◽

Takeshi Sugaya ◽

Yugo Shibagaki ◽

Takashi Yasuda ◽

...

Keyword(s):

Fatty Acid ◽

Angiotensin Ii ◽

Renal Injury ◽

Fatty Acid Binding Protein ◽

Ang Ii ◽

Fatty Acid Binding ◽

Renoprotective Effect ◽

Acid Binding Protein ◽

Ras Activation ◽

Tubulointerstitial Damage

The aim of this study was to assess the renoprotective effect of renal human liver-type fatty acid binding protein (hL-FABP) and angiotensin II (ANG II) type 1A receptor (AT1a) loss in renal injury caused by renin-angiotensin system (RAS) activation. We established hL-FABP chromosomal transgenic mice (L-FABP+/−AT1a+/+), crossed the L-FABP+/−AT1a+/+ with AT1a knockdown homo mice (L-FABP−/−AT1a−/−), and generated L-FABP+/−AT1a hetero mice (L-FABP+/−AT1a+/−). After the back-cross of these cubs, L-FABP+/−AT1a−/− were obtained. To activate the renal RAS, wild-type mice (L-FABP−/−AT1a+/+), L-FABP+/−AT1a+/+, L-FABP−/−AT1a+/−, L-FABP+/−AT1a+/−, L-FABP−/−AT1a−/−, and L-FABP+/−AT1a−/− were administered high-dose systemic ANG II infusion plus a high-salt diet for 28 days. In the L-FABP−/−AT1a+/+, RAS activation (L-FABP−/−AT1a+/+RAS) caused hypertension and tubulointerstitial damage. In the L-FABP+/−AT1a+/+RAS, tubulointerstitial damage was significantly attenuated compared with L-FABP−/−AT1a+/+RAS. In the AT1a partial knockout (AT1a+/−) or complete knockout (AT1a−/−) mice, reduction of AT1a expression led to a significantly lower degree of renal injury compared with L-FABP−/−AT1a+/+RAS or L-FABP+/−AT1a+/+RAS mice. Renal injury in L-FABP+/−AT1a+/−RAS mice was significantly attenuated compared with L-FABP−/−AT1a+/−RAS mice. In both L-FABP−/−AT1a−/−RAS and L-FABP+/−AT1a−/−RAS mice, renal damage was rarely found. The degrees of renal hL-FABP expression and urinary hL-FABP levels increased by RAS activation and gradually decreased along with reduction of AT1a expression levels. In conclusion, in this mouse model, renal hL-FABP expression and a decrease in AT1a expression attenuated tubulointerstitial damage due to RAS activation.

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Systolic blood pressure and fatty acid-binding protein 4 predict pregnancy-induced hypertension in overweight nulliparous women

Endocrine Abstracts ◽

10.1530/endoabs.35.p637 ◽

2014 ◽

Author(s):

Anna Tuuri ◽

Matti Jauhiainen ◽

Risto Kaaja

Keyword(s):

Blood Pressure ◽

Fatty Acid ◽

Systolic Blood Pressure ◽

Fatty Acid Binding Protein ◽

Binding Protein ◽

Pregnancy Induced Hypertension ◽

Fatty Acid Binding ◽

Acid Binding Protein ◽

Nulliparous Women ◽

Induced Hypertension

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Epidermal Fatty Acid-Binding Protein 5 (FABP5) Involvement in Alpha-Synuclein-Induced Mitochondrial Injury under Oxidative Stress

Biomedicines ◽

10.3390/biomedicines9020110 ◽

2021 ◽

Vol 9 (2) ◽

pp. 110

Author(s):

Yifei Wang ◽

Yasuharu Shinoda ◽

An Cheng ◽

Ichiro Kawahata ◽

Kohji Fukunaga

Keyword(s):

Oxidative Stress ◽

Fatty Acid ◽

Mitochondrial Dysfunction ◽

Fatty Acid Binding Protein ◽

Binding Protein ◽

Alpha Synuclein ◽

Fatty Acid Binding ◽

Mitochondrial Injury ◽

Mitochondrial Respiratory Chain Complex ◽

Acid Binding Protein

The accumulation of α-synuclein (αSyn) has been implicated as a causal factor in the pathogenesis of Parkinson’s disease (PD). There is growing evidence that supports mitochondrial dysfunction as a potential primary cause of dopaminergic neuronal death in PD. Here, we focused on reciprocal interactions between αSyn aggregation and mitochondrial injury induced by oxidative stress. We further investigated whether epidermal fatty acid-binding protein 5 (FABP5) is related to αSyn oligomerization/aggregation and subsequent disturbances in mitochondrial function in neuronal cells. In the presence of rotenone, a mitochondrial respiratory chain complex I inhibitor, co-overexpression of FABP5 with αSyn significantly decreased the viability of Neuro-2A cells compared to that of αSyn alone. Under these conditions, FABP5 co-localized with αSyn in the mitochondria, thereby reducing mitochondrial membrane potential. Furthermore, we confirmed that pharmacological inhibition of FABP5 by its ligand prevented αSyn accumulation in mitochondria, which led to cell death rescue. These results suggested that FABP5 is crucial for mitochondrial dysfunction related to αSyn oligomerization/aggregation in the mitochondria induced by oxidative stress in neurons.

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