Alteration Of Renal Tubular Cell Energetics After Exposure To Toxicants

FIGURE 15-20

Mechanisms by which nephrotoxicants can alter renal tubular cell energetics.

Decreased oxygen delivery secondary to vasoconstriction Inhibition of mitochondrial respiration Increased tubular cell oxygen consumption

Substrates

Cephaloridine

Bromohydroquinone

Dichlorovinyl-L-cysteine Tetrafluoroethyl-L-cysteine Pentachlorobutadienyl-L-cysteine Citrinin Ochratoxin A Hg2+ CN

Pentachlorobutadienyl-L-cysteine

Citrinin

FCCP

Substrates

Cephaloridine

Bromohydroquinone

Dichlorovinyl-L-cysteine Tetrafluoroethyl-L-cysteine Pentachlorobutadienyl-L-cysteine Citrinin Ochratoxin A Hg2+ CN

Pentachlorobutadienyl-L-cysteine

Citrinin

FCCP

Atractyloside Ochratoxin A

Atractyloside Ochratoxin A

Oligomycin

Ochratoxin A

Inner membrane Outer membrane

Some of the mitochondrial targets of nephro-toxicants: 1) nicotinamide adenine dinu-cleotide (NADH) dehydrogenase; 2) succinate dehydrogenase; 3) coenzyme Q-cytochrome C reductase; 4) cytochrome C; 5) cytochrome C oxidase; 6) cytochrome Aa3; 7) H+-Pi contransporter; 8) F0Fi-ATPase; 9) adenine triphosphate/diphosphate (ATP/ADP) translocase; 10) protonophore (uncoupler); 11) substrate transporters.

Disruption of ion homeostasis

FIGURE 15-22

Early ion movements after mitochondrial dysfunction. A, A control renal proximal tubular cell. Within minutes of mitochondrial inhibition (eg, by antimycin A), ATP levels drop, resulting in inhibition of the Na+, K+-ATPase. B, Consequently, Na+ influx, K+ efflux, membrane depolarization, and a limited degree of cell swelling occur.

FIGURE 15-22

Early ion movements after mitochondrial dysfunction. A, A control renal proximal tubular cell. Within minutes of mitochondrial inhibition (eg, by antimycin A), ATP levels drop, resulting in inhibition of the Na+, K+-ATPase. B, Consequently, Na+ influx, K+ efflux, membrane depolarization, and a limited degree of cell swelling occur.

FIGURE 15-23

A graphic of the phenomena diagrammed in Figure 15-22.

Cr^p Cl

Cr^p Cl

A Antimycin A K+

B Antimycin A

B Antimycin A

FIGURE 15-24

The late ion movements after mitochondrial dysfunction that leads to cell death/lysis. A, Cl- influx occurs as a distinct step subsequent to Na+ influx and K+ efflux. B, Following Cl- influx, additional Na+ and water influx occur resulting in terminal cell swelling. Ultimately cell lysis occurs.

FIGURE 15-25

A graph of the phenomena depicted in Figures 15-22 through 1524, illustrating the complete temporal sequence of events following mitochondrial dysfunction. QO2—oxygen consumption.

Disregulation of regulatory enzymes

FIGURE 15-26

A simplified schematic drawing of the regulation of cytosolic free Ca2+.

Was this article helpful?

0 0

Post a comment